1 00:00:05,600 --> 00:00:10,080 >>WELCOME TO THE DNA REPAIR 2 00:00:10,080 --> 00:00:14,520 INTEREST GROUP CONFERENCE 3 00:00:14,520 --> 00:00:18,840 DR. SARASIN, THIS IS ACTUALLY 4 00:00:18,840 --> 00:00:19,960 HIS SECOND PRESENTATION TO OUR 5 00:00:19,960 --> 00:00:22,080 GROUP, THE FIRST WAS IN 2003. 6 00:00:22,080 --> 00:00:25,080 AND YOU CAN ACTUALLY SEE WHAT HE 7 00:00:25,080 --> 00:00:28,520 LOOKED LIKE THEN, AND WHAT I 8 00:00:28,520 --> 00:00:29,440 LOOKED LIKE THEN. 9 00:00:29,440 --> 00:00:29,760 [LAUGHTER] 10 00:00:29,760 --> 00:00:34,480 SEVENTEEN YEARS AGO, HE WAS 11 00:00:34,480 --> 00:00:36,960 TALKING ABOUT XP VARIANT, HOW HE 12 00:00:36,960 --> 00:00:40,680 WAS GOING TO CURE XPC AT THAT 13 00:00:40,680 --> 00:00:40,880 POINT. 14 00:00:40,880 --> 00:00:46,280 WE GO BACK A LITTLE BIT. 15 00:00:46,280 --> 00:00:52,320 HE IS EMERITUS RESEARCH 16 00:00:52,320 --> 00:00:54,040 DIRECTOR, IN FRANCE, ALSO 17 00:00:54,040 --> 00:01:00,920 DIRECTOR OF LABORATORY OF 18 00:01:00,920 --> 00:01:03,720 DIAGNOSIS DNA REPAIR DISEASES, 19 00:01:03,720 --> 00:01:07,360 AND FROM HIS OFFICE YOU COULD 20 00:01:07,360 --> 00:01:14,200 SEE THE EIFFEL TOWER. 21 00:01:14,200 --> 00:01:16,200 HE WAS ORIGINALLY FROM -- HE GOT 22 00:01:16,200 --> 00:01:22,760 HIS Ph.D. DEGREE, UNIVERSITY 23 00:01:22,760 --> 00:01:27,960 OF PARIS, STUDYING BACTERIA, HE 24 00:01:27,960 --> 00:01:32,480 WORKED -- CONTINUED WITH 25 00:01:32,480 --> 00:01:36,600 (INDISCERNIBLE), SOS PATHWAY, 26 00:01:36,600 --> 00:01:43,320 INTERNATIONAL SCIENTIST, WHO 27 00:01:43,320 --> 00:01:52,040 WENT TO STANFORD AND AFLOTOXIN 28 00:01:52,040 --> 00:02:04,160 TO XERODERM, MOVED SOUTH TO RIO 29 00:02:04,160 --> 00:02:06,320 DE JANEIRO, BRAZIL, VISITING 30 00:02:06,320 --> 00:02:11,520 PROFESSOR, A MEMBER OF MANY 31 00:02:11,520 --> 00:02:11,840 ORGANIZATIONS. 32 00:02:11,840 --> 00:02:18,960 HE WAS IN THE (INDISCERNIBLE) 33 00:02:18,960 --> 00:02:21,240 FOR THE EUROPEAN SPACE AGENCY, 34 00:02:21,240 --> 00:02:25,520 THINGS HE DOES ALL OVER SPACE, 35 00:02:25,520 --> 00:02:27,600 INTERNATIONAL ASSOCIATION OF 36 00:02:27,600 --> 00:02:30,000 ENVIRONMENTAL MUTAGENESIS AND 37 00:02:30,000 --> 00:02:32,840 STUDIES CHAIRMAN OF SCIENTIFIC 38 00:02:32,840 --> 00:02:37,000 COUNCIL FOR CANCER AND HIS MAIN 39 00:02:37,000 --> 00:02:40,400 INTERESTS ARE DIAGNOSIS OF 40 00:02:40,400 --> 00:02:42,120 REPAIR DEFICIENCY DISEASES, AND 41 00:02:42,120 --> 00:02:47,200 OTHERS, HE HAS A NUMBER OF 42 00:02:47,200 --> 00:02:50,200 FIRSTS IN DIAGNOSING, INCLUDING 43 00:02:50,200 --> 00:02:51,960 PRENATAL DIAGNOSIS, AND 44 00:02:51,960 --> 00:02:53,960 (INDISCERNIBLE) FOR MANY YEARS, 45 00:02:53,960 --> 00:02:55,520 SO TODAY HE WILL BE TALKING 46 00:02:55,520 --> 00:03:01,600 ABOUT NOT ONLY THE SKIN CANCER, 47 00:03:01,600 --> 00:03:03,920 XERODERMA AROUND THE WORLD, NEW 48 00:03:03,920 --> 00:03:07,640 STUDIES OF INTERNAL CANCERS AND 49 00:03:07,640 --> 00:03:10,080 NOW WE'LL HAVE A FEW WORDS. 50 00:03:10,080 --> 00:03:12,880 >> TO ADD TO THAT 51 00:03:12,880 --> 00:03:15,200 INTRODUCTION, I HAVE 52 00:03:15,200 --> 00:03:17,280 KNOWN ALAIN SINCE DAYS AT 53 00:03:17,280 --> 00:03:18,480 STANFORD AND REALLY TREMENDOUSLY 54 00:03:18,480 --> 00:03:20,560 ENJOYED YOUR WORK AND MEETING 55 00:03:20,560 --> 00:03:23,080 YOU ON MANY OCCASIONS, AND YOU 56 00:03:23,080 --> 00:03:25,040 HAVE MADE GREAT STRIDES IN THE 57 00:03:25,040 --> 00:03:30,040 XP AND RELATED FIELDS AND VERY 58 00:03:30,040 --> 00:03:31,880 BROAD-BASED, IT'S A PLEASURE TO 59 00:03:31,880 --> 00:03:36,920 HAVE YOU HERE, AND THEN I JUST 60 00:03:36,920 --> 00:03:39,640 WANTED TO MENTION THAT WE HAVE 61 00:03:39,640 --> 00:03:41,600 QUESTIONS, IF ANY OF THE PEOPLE 62 00:03:41,600 --> 00:03:43,040 ATTENDING WOULD LIKE TO ASK A 63 00:03:43,040 --> 00:03:44,440 QUESTION PLEASE TYPE IT ON THE 64 00:03:44,440 --> 00:03:47,160 CHAT BOX AND KEN AND I WILL READ 65 00:03:47,160 --> 00:03:50,560 THEM UP FOR ALAIN AND YOU, AFTER 66 00:03:50,560 --> 00:03:53,760 THE TALK. 67 00:03:53,760 --> 00:03:54,120 THANK YOU VERY MUCH. 68 00:03:54,120 --> 00:03:55,920 >> OKAY. 69 00:03:55,920 --> 00:03:57,720 TAKE IT AWAY, ALAIN. 70 00:03:57,720 --> 00:04:01,960 >>THANK YOU FOR THE INVITATION 71 00:04:01,960 --> 00:04:04,640 TO COME TO WASHINGTON, BUT 72 00:04:04,640 --> 00:04:06,000 UNFORTUNATELY I'M STILL IN PARIS 73 00:04:06,000 --> 00:04:09,240 BECAUSE OF THE COVID, OF COURSE. 74 00:04:09,240 --> 00:04:11,880 YOU TOLD ME, YOU SAID THAT FROM 75 00:04:11,880 --> 00:04:14,160 MY OFFICE I CAN SEE THE EIFFEL 76 00:04:14,160 --> 00:04:15,840 TOWER, WHICH IS STILL TRUE, AND 77 00:04:15,840 --> 00:04:17,800 I SHOWED YOU A PICTURE THAT I 78 00:04:17,800 --> 00:04:20,160 CANNOT SEE FROM MY OFFICE, WHICH 79 00:04:20,160 --> 00:04:23,000 IS A PICTURE OF ONE OF THE 80 00:04:23,000 --> 00:04:25,200 ISLANDS I'M GOING TO TALK ABOUT 81 00:04:25,200 --> 00:04:26,920 IN A MINUTE, WHICH IS CALLED 82 00:04:26,920 --> 00:04:27,560 (INDISCERNIBLE). 83 00:04:27,560 --> 00:04:30,760 SO I'M GOING TO OF COURSE AS YOU 84 00:04:30,760 --> 00:04:35,680 MIGHT EXPECT TALK ABOUT XPs 85 00:04:35,680 --> 00:04:36,880 AND NUCLEOTIDE REPAIR. 86 00:04:36,880 --> 00:04:41,720 SINCE DR. KRAMER ASKED ME TO 87 00:04:41,720 --> 00:04:43,560 EXPLAIN A LITTLE BIT SOME 88 00:04:43,560 --> 00:04:45,080 AFRICAN COUNTRY AND FROM BRAZIL 89 00:04:45,080 --> 00:04:48,280 SO I WILL GIVE YOU AN EXAMPLE 90 00:04:48,280 --> 00:04:54,080 HOW WE CAN DO HISTORY AND 91 00:04:54,080 --> 00:04:55,720 GEOGRAPHY AND BRING GENE 92 00:04:55,720 --> 00:04:58,680 MUTATION ANALYSIS AT THE SAME 93 00:04:58,680 --> 00:04:58,960 TIME. 94 00:04:58,960 --> 00:05:03,960 THEN I WILL SWITCH TO MY MAIN 95 00:05:03,960 --> 00:05:06,560 TOPIC, RISK FACTOR OF DEVELOPING 96 00:05:06,560 --> 00:05:07,920 INTERNAL TUMORS IN XP PATIENTS, 97 00:05:07,920 --> 00:05:12,560 AND WHAT IS A MUTATIONAL 98 00:05:12,560 --> 00:05:27,680 LANDSCAPE OF A METALLURGY 99 00:05:27,680 --> 00:05:32,160 MALIGNANCY, MUCH MORE COMMON IN 100 00:05:32,160 --> 00:05:33,040 NORTH AFRICA, JAPAN, PAKISTAN, 101 00:05:33,040 --> 00:05:34,480 RARE IN EUROPE. 102 00:05:34,480 --> 00:05:37,760 THE PATIENTS ARE UV SENSITIVE 103 00:05:37,760 --> 00:05:39,720 AND THEY GET SKIN DISORDER, THIS 104 00:05:39,720 --> 00:05:44,000 IS DUE TO THE FACT THEY HAVE 105 00:05:44,000 --> 00:05:47,040 DEFICIENCY IN GENE REPAIR IN 106 00:05:47,040 --> 00:05:48,920 NUCLEOTIDE REPAIR, MUTATION IN 107 00:05:48,920 --> 00:05:52,760 ONE OF THE SEVEN XP GENES OR DUE 108 00:05:52,760 --> 00:05:58,800 TO MUTATION IN THE POLYMERASE, 109 00:05:58,800 --> 00:05:59,120 XP VARIANT. 110 00:05:59,120 --> 00:06:02,680 IF THESE PATIENTS ARE NOT FULLY 111 00:06:02,680 --> 00:06:04,120 PROTECTED FROM SUN EXPOSURE, 112 00:06:04,120 --> 00:06:07,880 THEY WILL DEVELOP VERY HIGH 113 00:06:07,880 --> 00:06:09,400 FREQUENCY OF UV-INDUCED SKIN 114 00:06:09,400 --> 00:06:11,520 CANCER, UNFORTUNATELY WILL HAVE 115 00:06:11,520 --> 00:06:14,440 A SHORT LIFETIME ALSO. 116 00:06:14,440 --> 00:06:16,080 SO, WHAT ABOUT MY RELATIONSHIP 117 00:06:16,080 --> 00:06:20,160 WITH AFRICA AND BRAZIL? 118 00:06:20,160 --> 00:06:24,720 I WILL START HERE WITH THE 119 00:06:24,720 --> 00:06:29,320 COMORES, THE WHOLE ISLAND WHICH 120 00:06:29,320 --> 00:06:31,560 FORMED THE COMORIAN ARCHIPELAGO, 121 00:06:31,560 --> 00:06:35,120 THESE ISLANDS ARE LOCATED IN 122 00:06:35,120 --> 00:06:41,360 BETWEEN THE EAST AFRICAN COAST, 123 00:06:41,360 --> 00:06:42,760 YOU CAN RECOGNIZE HERE 124 00:06:42,760 --> 00:06:44,080 MOZAMBIQUE, KENYA, AND HERE WE 125 00:06:44,080 --> 00:06:48,760 SEE THE BIG ISLAND OF 126 00:06:48,760 --> 00:06:49,040 MADAGASCAR. 127 00:06:49,040 --> 00:06:50,600 INTERESTINGLY, THE EQUATOR IS 128 00:06:50,600 --> 00:06:52,320 VERY, VERY CLOSE TO THESE 129 00:06:52,320 --> 00:06:54,640 ISLANDS, WHICH IS VERY BAD NEWS 130 00:06:54,640 --> 00:06:56,560 FOR XP PATIENTS. 131 00:06:56,560 --> 00:06:59,920 SO, I'VE BEEN THERE BECAUSE 132 00:06:59,920 --> 00:07:02,200 THESE WHOLE ISLANDS WERE FRENCH 133 00:07:02,200 --> 00:07:05,720 40 YEARS AGO. 134 00:07:05,720 --> 00:07:08,000 NOW IT'S A FREE WHITE ISLAND, 135 00:07:08,000 --> 00:07:09,560 AND THE YELLOW ONE, THIS IS THE 136 00:07:09,560 --> 00:07:12,920 FIRST PICTURE I SHOWED YOU, A 137 00:07:12,920 --> 00:07:13,760 FRENCH DEPARTMENT. 138 00:07:13,760 --> 00:07:15,400 AND XP PATIENTS HAVE BEEN 139 00:07:15,400 --> 00:07:19,600 REPORTED IN SOME OF THE ISLANDS, 140 00:07:19,600 --> 00:07:22,600 SO I WENT THERE AND I ANALYZED, 141 00:07:22,600 --> 00:07:26,760 I DID SOME CLASSICAL ANALYSIS OF 142 00:07:26,760 --> 00:07:29,160 XP PATIENTS, WE FOUND IN THIS 143 00:07:29,160 --> 00:07:34,280 ISLAND PROBABLY ONE OF THE 144 00:07:34,280 --> 00:07:45,960 HIGHEST INCIDENCE OF XP, 1 IN 145 00:07:45,960 --> 00:07:47,360 5,000, THE MUTATION, EXOME 12, 146 00:07:47,360 --> 00:07:55,280 AT THE TIME WE PUBLISHED THIS, 147 00:07:55,280 --> 00:07:56,800 THE COMORIAN MUTATION, THE 148 00:07:56,800 --> 00:07:58,240 MUTATION WAS NOT DISCOVERED 149 00:07:58,240 --> 00:08:01,160 EVERYWHERE ELSE IN THE WORLD. 150 00:08:01,160 --> 00:08:03,600 WE CALCULATE THE AGE OF MUTATION 151 00:08:03,600 --> 00:08:07,400 INSIDE THE ISLAND, IF WE BELIEVE 152 00:08:07,400 --> 00:08:12,920 THE ISLAND IS CLOSE BUBBLE, WE 153 00:08:12,920 --> 00:08:14,440 CALCULATE THE AGE TO BE 800 154 00:08:14,440 --> 00:08:14,960 YEARS OLD. 155 00:08:14,960 --> 00:08:17,800 WE'LL COME BACK TO THAT. 156 00:08:17,800 --> 00:08:19,880 HIGH INCIDENCE OF XPs IS 157 00:08:19,880 --> 00:08:22,160 ESSENTIALLY DUE TO THE CLOSE 158 00:08:22,160 --> 00:08:23,520 ENVIRONMENT OF THE ISLAND, ALSO 159 00:08:23,520 --> 00:08:27,080 TO THE FACT THAT THE PEOPLE HAVE 160 00:08:27,080 --> 00:08:32,760 A REMARKABLE DEGREE OF 161 00:08:32,760 --> 00:08:35,760 INBREEDING, STILL POLYGAMY IN 162 00:08:35,760 --> 00:08:37,560 SOME ISLANDS HERE. 163 00:08:37,560 --> 00:08:40,360 THESE PATIENTS ARE BLACK SKINNED 164 00:08:40,360 --> 00:08:42,640 PATIENTS, I FOUND THIS GUY MORE 165 00:08:42,640 --> 00:08:45,040 THAN TEN YEARS AGO, NOW BACK IN 166 00:08:45,040 --> 00:08:49,360 PARIS, AND THIS IS THE SAME GUY, 167 00:08:49,360 --> 00:08:55,120 AT 7 YEARS DIFFERENCE, YOU CAN 168 00:08:55,120 --> 00:08:59,320 RECOGNIZE THE XP DISEASE IS HIGH 169 00:08:59,320 --> 00:09:00,200 MUTATION DISEASE, INCREASE 170 00:09:00,200 --> 00:09:04,600 MUTATION IN 7 YEARS BUT HIGH 171 00:09:04,600 --> 00:09:09,760 MUTATION IN BLACK SKIN, IN FACT 172 00:09:09,760 --> 00:09:13,600 XP IS BOTH (INDISCERNIBLE) 173 00:09:13,600 --> 00:09:14,160 DISEASE. 174 00:09:14,160 --> 00:09:15,680 USUALLY BLACK PEOPLE ARE 175 00:09:15,680 --> 00:09:18,360 RELATIVELY PROTECTED FROM SKIN 176 00:09:18,360 --> 00:09:23,280 CANCER BUT STILL XP PATIENTS 177 00:09:23,280 --> 00:09:23,960 HAVE SKIN CANCER, PARTICULARLY 178 00:09:23,960 --> 00:09:29,320 IN THE TOP OF THE HEAD HERE, AND 179 00:09:29,320 --> 00:09:29,960 INTERESTINGLY THEY DEVELOP 180 00:09:29,960 --> 00:09:31,720 TUMORS ON THE TIP OF THE TONGUE 181 00:09:31,720 --> 00:09:33,760 AS WELL, BECAUSE THE TONGUE IS 182 00:09:33,760 --> 00:09:35,840 NOT EXPOSED -- IS EXPOSED TO 183 00:09:35,840 --> 00:09:39,920 SUN, AND IS NOT PROTECTED BY 184 00:09:39,920 --> 00:09:41,560 MELANIN. 185 00:09:41,560 --> 00:09:43,680 MOST OF THE PATIENTS GET ON THE 186 00:09:43,680 --> 00:09:46,920 TIP OF THE TONGUE. 187 00:09:46,920 --> 00:09:47,680 AND UNFORTUNATELY, THESE 188 00:09:47,680 --> 00:09:49,400 PATIENTS DON'T PROTECT THEIR 189 00:09:49,400 --> 00:09:51,720 EYES, ALTHOUGH WE BRING THEM 190 00:09:51,720 --> 00:09:55,320 SUNGLASSES EVERY YEAR, OR MOST, 191 00:09:55,320 --> 00:09:58,400 AND SO USUALLY THEY BECOME BLIND 192 00:09:58,400 --> 00:10:04,120 BEFORE -- BETWEEN THE AGE OF 10 193 00:10:04,120 --> 00:10:04,560 OR 15. 194 00:10:04,560 --> 00:10:07,720 SO, WE THOUGHT THE MUTATION WAS 195 00:10:07,720 --> 00:10:09,600 SPECIFIC OF COMORES, A COUPLE 196 00:10:09,600 --> 00:10:13,960 YEARS AGO THE GROUP OF DR. 197 00:10:13,960 --> 00:10:16,360 KUKURU IN PRETORIA, HERE, THE 198 00:10:16,360 --> 00:10:20,160 RED POINT HERE, IN SOUTH AFRICA, 199 00:10:20,160 --> 00:10:27,880 ALSO IN ZIMBABWE, WHICH IS HERE, 200 00:10:27,880 --> 00:10:31,440 IN KENYA WE FOUND A PATIENT, IN 201 00:10:31,440 --> 00:10:34,560 MOZAMBIQUE WE FOUND PATIENT, 202 00:10:34,560 --> 00:10:39,480 ANALYZED, THE PATIENT IN EAST 203 00:10:39,480 --> 00:10:41,840 AFRICA HAVE XPC MUTATION OF 204 00:10:41,840 --> 00:10:42,360 COMORES. 205 00:10:42,360 --> 00:10:45,800 WHEN WE CALCULATE AGE OF 206 00:10:45,800 --> 00:10:51,160 MUTATION, AGE OF MUTATION WAS 207 00:10:51,160 --> 00:10:53,160 ABOUT 1100 YEARS, WHICH MEANS 208 00:10:53,160 --> 00:10:54,680 MUTATION IN EAST AFRICA WAS 209 00:10:54,680 --> 00:10:57,320 OLDER THAN THE MUTATION IN 210 00:10:57,320 --> 00:11:01,480 COMORES, INDEED WHEN WE LOOK AT 211 00:11:01,480 --> 00:11:05,760 HISTORY OF COMORES, THE ISLANDS 212 00:11:05,760 --> 00:11:07,800 WHERE PEOPLE BY EAST 213 00:11:07,800 --> 00:11:09,120 AFRICAN-BORN POPULATION AROUND 214 00:11:09,120 --> 00:11:11,200 THE 7th AND 10th CENTURY, 215 00:11:11,200 --> 00:11:17,320 AND SHOULD HAVE BEEN PEOPLE BY 216 00:11:17,320 --> 00:11:24,840 SOME XP HETEROZYGOTE, GIVE RISE 217 00:11:24,840 --> 00:11:29,160 TO HIGH XP DUE TO ISLAND 218 00:11:29,160 --> 00:11:29,640 ISOLATION. 219 00:11:29,640 --> 00:11:32,840 A FEW YEARS AGO THE PAPER WAS 220 00:11:32,840 --> 00:11:38,160 PUBLISHED, LAST YEAR DR. WALID 221 00:11:38,160 --> 00:11:42,760 IN PAKISTAN REPORTED A GROUP OF 222 00:11:42,760 --> 00:11:45,280 XP PATIENTS, THESE PATIENTS HAVE 223 00:11:45,280 --> 00:11:46,520 COMORIAN MUTATION. 224 00:11:46,520 --> 00:11:51,200 HERE AGAIN EAST AFRICAN COAST, 225 00:11:51,200 --> 00:11:52,520 AND SO GEOGRAPHY IS STILL THE 226 00:11:52,520 --> 00:11:55,920 SAME SO HERE YOU HAVE THE EAST 227 00:11:55,920 --> 00:11:59,360 AFRICAN COUNTRY, AND HERE YOU 228 00:11:59,360 --> 00:12:06,160 HAVE THE ARABIC HERE, AND HERE 229 00:12:06,160 --> 00:12:09,800 YOU HAVE SOUTH IRAN, AND THE 230 00:12:09,800 --> 00:12:13,600 PLACE WHICH AT THAT TIME WAS 231 00:12:13,600 --> 00:12:16,840 VERY -- THE CAPITAL OF IRAN, 232 00:12:16,840 --> 00:12:19,280 WHAT IS IRAN NOW. 233 00:12:19,280 --> 00:12:21,000 IN FACT BETWEEN 11th AND 234 00:12:21,000 --> 00:12:23,760 13th CENTURY, THIS IS HISTORY, 235 00:12:23,760 --> 00:12:28,680 THE ARABS WERE DOWN BY BOAT FROM 236 00:12:28,680 --> 00:12:30,320 THIS ARABIC COUNTRY TO SOUTH 237 00:12:30,320 --> 00:12:34,160 ALONG THE EAST COAST OF AFRICA. 238 00:12:34,160 --> 00:12:37,640 AND THEY WERE SAILORS, TRADERS, 239 00:12:37,640 --> 00:12:40,160 DOING BUSINESS WITH THE 240 00:12:40,160 --> 00:12:41,360 DIFFERENT EAST AFRICAN COUNTRY, 241 00:12:41,360 --> 00:12:44,440 AT THE SAME TIME WHEN THEY WENT 242 00:12:44,440 --> 00:12:46,720 BACK HOME THEY WENT BY TAKING 243 00:12:46,720 --> 00:12:52,320 THE BLACK PEOPLE AS SLAVES, 244 00:12:52,320 --> 00:12:53,960 BLACK MEN AS SLAVE, TAKING BLACK 245 00:12:53,960 --> 00:12:55,400 WOMEN AS SPOUSE, OKAY? 246 00:12:55,400 --> 00:12:59,840 SO A LOT OF BLACK PEOPLE FROM 247 00:12:59,840 --> 00:13:01,720 THE EAST COAST COUNTRY AS WELL 248 00:13:01,720 --> 00:13:06,840 AS SOME ISLAND LIKE ZANZIBAR 249 00:13:06,840 --> 00:13:10,760 WHICH IS HERE THE BLACK WENT 250 00:13:10,760 --> 00:13:13,400 BACK TO SOUTH IRAN AND THESE 251 00:13:13,400 --> 00:13:17,120 PATIENTS WERE BEING DESCRIBED TO 252 00:13:17,120 --> 00:13:18,720 HAVE COMORIAN MUTATION, ALSO 253 00:13:18,720 --> 00:13:20,760 HAPLOTYPE THAT WE CAN FIND IN 254 00:13:20,760 --> 00:13:21,680 EAST AFRICA. 255 00:13:21,680 --> 00:13:27,560 SO WHAT WE BELIEVE IS THAT THE 256 00:13:27,560 --> 00:13:29,480 BLACK PEOPLE WERE TAKEN AS SLAVE 257 00:13:29,480 --> 00:13:32,360 HERE, NOW LIVING THERE. 258 00:13:32,360 --> 00:13:34,440 AND INTERESTINGLY THE XP FROM 259 00:13:34,440 --> 00:13:36,560 PAKISTAN ARE LIVING AS NOMAD 260 00:13:36,560 --> 00:13:39,920 TRIBES, AND THEY ARE LIVING IN 261 00:13:39,920 --> 00:13:42,840 BETWEEN SOUTH IRAN AND PAKISTAN 262 00:13:42,840 --> 00:13:47,040 ACCORDING TO THE TIME OF YEAR. 263 00:13:47,040 --> 00:13:48,360 AND FINALLY, TO MAKE A LONG 264 00:13:48,360 --> 00:13:49,640 STORY SHORT, I JUST WANTS TO 265 00:13:49,640 --> 00:13:52,960 REMIND YOU THAT THERE WAS A 266 00:13:52,960 --> 00:13:54,920 SEA-GOING SLAVE TRADE BETWEEN 267 00:13:54,920 --> 00:13:57,840 THE WEST COAST OF AFRICA AND THE 268 00:13:57,840 --> 00:14:02,480 SOUTH AMERICA AND CENTRAL 269 00:14:02,480 --> 00:14:04,880 AMERICA AND NORTH AMERICA, AND 270 00:14:04,880 --> 00:14:06,960 WHEN THE SLAVE TRADE WAS 271 00:14:06,960 --> 00:14:09,560 FORBIDDEN ALONG THE COAST, THE 272 00:14:09,560 --> 00:14:12,120 WEST COAST, THEN THE PEOPLE WENT 273 00:14:12,120 --> 00:14:14,880 FROM THE EAST COAST COUNTRIES 274 00:14:14,880 --> 00:14:18,960 AND AT THAT TIME MOZAMBIQUE 275 00:14:18,960 --> 00:14:20,360 WHICH HERE, MOZAMBIQUE WAS 276 00:14:20,360 --> 00:14:26,040 PORTUGUESE, SO THERE WAS SLAVE 277 00:14:26,040 --> 00:14:33,360 TRADE BETWEEN MOZAMBIQUE, IT'S 278 00:14:33,360 --> 00:14:35,360 BEEN CALCULATED THAT ABOUT 20% 279 00:14:35,360 --> 00:14:38,760 OF BLACK AFRICAN SLAVE IN BRAZIL 280 00:14:38,760 --> 00:14:40,600 CAME FROM EAST AFRICA, AND WHEN 281 00:14:40,600 --> 00:14:43,760 THESE PEOPLE CAME FROM EAST 282 00:14:43,760 --> 00:14:46,760 AFRICA TO RIO DE JANEIRO, FROM 283 00:14:46,760 --> 00:14:52,480 THE COAST COMING FROM 284 00:14:52,480 --> 00:14:53,600 MOZAMBIQUE. 285 00:14:53,600 --> 00:14:55,040 WITH THE GROUP OF 286 00:14:55,040 --> 00:14:58,720 [SPEAKING FRENCH] AS NATIONAL 287 00:14:58,720 --> 00:15:01,400 INSTITUTE OF SAO PAULO, THE 288 00:15:01,400 --> 00:15:03,760 PROFESSOR AND DOCTOR IN MY LAB 289 00:15:03,760 --> 00:15:08,000 FROM UNIVERSITY OF SAN PAOLO, 290 00:15:08,000 --> 00:15:13,400 THEY LOCATED IN BRAZIL THE XPC 291 00:15:13,400 --> 00:15:14,960 PATIENT WITH COMORIAN MUTATION. 292 00:15:14,960 --> 00:15:21,760 MOST OF XP PATIENT ARE LOCATED 293 00:15:21,760 --> 00:15:24,560 HERE CLOSE TO RIO DE JANEIRO 294 00:15:24,560 --> 00:15:26,200 HARBOR, CLOSE TO SALVADORE, IN 295 00:15:26,200 --> 00:15:29,160 THE NORTHEAST OF BRAZIL, CLOSE 296 00:15:29,160 --> 00:15:31,920 TO RECIFE. 297 00:15:31,920 --> 00:15:36,320 SO WHAT I CALL THE AFRICAN XP 298 00:15:36,320 --> 00:15:39,280 MUTATION IS PROBABLY A MUTATION 299 00:15:39,280 --> 00:15:46,680 WHAT I CALL COMORIAN, WE SHOULD 300 00:15:46,680 --> 00:15:55,200 CALL IT XPC, 1100 YEARS AGO. 301 00:15:55,200 --> 00:15:57,720 THEN IT CAME FROM COMORES BY 302 00:15:57,720 --> 00:16:00,480 EAST AFRICAN PEOPLE WHICH WERE 303 00:16:00,480 --> 00:16:08,920 SOME OF THEM WERE HETEROZYGOUS. 304 00:16:08,920 --> 00:16:10,880 DURING THE ARABS, SOME BLACK 305 00:16:10,880 --> 00:16:13,280 PEOPLE WENT TO SOUTH IRAN, NOW 306 00:16:13,280 --> 00:16:16,640 LOCATED BETWEEN SOUTH IRAN, 307 00:16:16,640 --> 00:16:26,960 PAKISTAN, AND FINALLY TO A FEW 308 00:16:26,960 --> 00:16:28,360 CENTURIES AAGO DUE TO SLAVE 309 00:16:28,360 --> 00:16:29,800 TRADING WENT TO BRAZIL. 310 00:16:29,800 --> 00:16:32,360 TO ANSWER THE QUESTION, THIS IS 311 00:16:32,360 --> 00:16:36,160 ONE OF MY RELATIONSHIPS WITH 312 00:16:36,160 --> 00:16:40,440 BRAZIL, IT'S ONE OF THE 313 00:16:40,440 --> 00:16:42,280 IMPORTANT ONE. 314 00:16:42,280 --> 00:16:46,920 SO NOW WE SWITCH GEAR AND TALK 315 00:16:46,920 --> 00:16:48,680 ABOUT AFRICAN XP, VERY IMPORTANT 316 00:16:48,680 --> 00:16:55,000 SUBJECT FOR THE XP PATIENT NOW. 317 00:16:55,000 --> 00:16:57,160 XP PATIENTS NOW LIVE LONGER IN 318 00:16:57,160 --> 00:16:58,560 DEVELOPING COUNTRIES BECAUSE 319 00:16:58,560 --> 00:17:02,360 THEY ARE VERY WELL EDUCATED IN 320 00:17:02,360 --> 00:17:04,360 TERMS OF UNDERSTANDING THEIR 321 00:17:04,360 --> 00:17:08,840 DISEASE AND UNDERSTANDING WHAT 322 00:17:08,840 --> 00:17:12,560 THEY SHOULD DO TO BE WITH SUN 323 00:17:12,560 --> 00:17:14,400 EXPOSURE, AND ALSO MEDICAL 324 00:17:14,400 --> 00:17:16,680 DOCTOR AND FAMILIES ARE BETTER 325 00:17:16,680 --> 00:17:16,960 EDUCATED. 326 00:17:16,960 --> 00:17:19,960 AS I'M GOING TO SHOW YOU AT THE 327 00:17:19,960 --> 00:17:21,560 END, AT LEAST IN FRANCE, BUT 328 00:17:21,560 --> 00:17:25,080 IT'S TRUE NOW IN SOME OTHER 329 00:17:25,080 --> 00:17:27,160 COUNTRY, WE HAVE DEVELOPED 330 00:17:27,160 --> 00:17:29,880 PROTECTION WHICH CAN PROTECT 331 00:17:29,880 --> 00:17:34,000 ALMOST TO 100% WHEN THESE 332 00:17:34,000 --> 00:17:36,200 PATIENTS GET OUTSIDE. 333 00:17:36,200 --> 00:17:38,040 XP PATIENTS ARE DEFICIENT, SO 334 00:17:38,040 --> 00:17:42,000 THE SKIN CELLS GIVE RISE TO SKIN 335 00:17:42,000 --> 00:17:45,160 CANCER, AND WHAT ABOUT INTERNAL 336 00:17:45,160 --> 00:17:45,400 ORGANS? 337 00:17:45,400 --> 00:17:47,360 SO, SOME REPORT HAVE BEEN 338 00:17:47,360 --> 00:17:50,760 PUBLISHED IN THE PAST, 339 00:17:50,760 --> 00:17:53,280 PARTICULARLY DR. KRAMER'S LAB, 340 00:17:53,280 --> 00:17:56,560 REPORTED 10 TO 20 HIGHER RISK OF 341 00:17:56,560 --> 00:18:00,520 BRAIN TUMORS IN XP, AND RECENTLY 342 00:18:00,520 --> 00:18:04,520 WE PUBLISHED PAPER LAST YEAR, 343 00:18:04,520 --> 00:18:07,360 REPORTED 13 XPC PATIENT WITH 344 00:18:07,360 --> 00:18:11,640 LEUKEMIA, AND DR. KRAMER'S LAB 345 00:18:11,640 --> 00:18:14,560 REPORTED THIS YEAR FOUR XPC 346 00:18:14,560 --> 00:18:16,160 PATIENT, AMERICAN XPC PATIENT 347 00:18:16,160 --> 00:18:19,800 WITH LEUKEMIA AS WELL. 348 00:18:19,800 --> 00:18:26,080 SO, WHAT I'VE DONE, TO COLLATE 349 00:18:26,080 --> 00:18:28,600 PUBLISHED IN THE LITERATURE 350 00:18:28,600 --> 00:18:30,200 BETWEEN 1958 AND NOW. 351 00:18:30,200 --> 00:18:30,880 WHY 1958? 352 00:18:30,880 --> 00:18:36,240 BECAUSE THIS IS THE FIRST REPORT 353 00:18:36,240 --> 00:18:39,840 WHEN XP PATIENT WITH LEUKEMIA 354 00:18:39,840 --> 00:18:45,680 AND BY DOING THAT I COLLATEN 89 355 00:18:45,680 --> 00:18:47,160 XP INTERNATIONALS CORRESPONDING 356 00:18:47,160 --> 00:18:54,680 TO 88 XP PATIENTS. 357 00:18:54,680 --> 00:18:58,160 THESE PATIENTS RECEIVED 358 00:18:58,160 --> 00:19:01,240 (INDISCERNIBLE) EARLIER, ALMOST 359 00:19:01,240 --> 00:19:03,160 50% OF XP ARE ORIGINATED FROM 360 00:19:03,160 --> 00:19:05,160 NORTH AFRICA, ALMOST ALL OF THEM 361 00:19:05,160 --> 00:19:06,800 ARE LIVING IN FRANCE, FRENCH, 362 00:19:06,800 --> 00:19:08,880 THEY LIVE IN FRANCE, OR THEY 363 00:19:08,880 --> 00:19:13,040 LIVE IN THE STATES, OR SOME IN 364 00:19:13,040 --> 00:19:13,280 BRAZIL. 365 00:19:13,280 --> 00:19:15,720 20% ARE FROM THE STATES. 366 00:19:15,720 --> 00:19:23,560 8% FROM JAPAN. 367 00:19:23,560 --> 00:19:25,760 WHEN KNOWN, WE DON'T HAVE 368 00:19:25,760 --> 00:19:28,520 COMPLEMENTATION, IN 1958 YOU CAN 369 00:19:28,520 --> 00:19:29,480 IMAGINE THE COMPLEMENTATION 370 00:19:29,480 --> 00:19:31,440 GROUP WERE NOT KNOWN, BUT WHEN 371 00:19:31,440 --> 00:19:34,720 WE KNOW THE COMPLEMENTATION 372 00:19:34,720 --> 00:19:43,400 GROUP 83%, THE VAST MAJORITY ARE 373 00:19:43,400 --> 00:19:46,880 XPC, THE VAST MAJORITY 374 00:19:46,880 --> 00:19:48,520 ORIGINATESSED FROM NORTH AFRICA, 375 00:19:48,520 --> 00:19:52,760 FOUND THE MUTATION, WHICH IS 376 00:19:52,760 --> 00:19:59,040 DELETION OF TG, IN THE EXOME, 377 00:19:59,040 --> 00:20:02,200 NORTH AFRICAN MUTATION. 378 00:20:02,200 --> 00:20:07,000 IF WE LOOK AT THE FREQUENCY OF 379 00:20:07,000 --> 00:20:11,080 THE TUMOR, XP PATIENTS, YOU CAN 380 00:20:11,080 --> 00:20:15,880 SEE THAT 30 INTERNATIONALS IN XP 381 00:20:15,880 --> 00:20:17,160 WHICH ARE HEMATOLOGICAL 382 00:20:17,160 --> 00:20:22,280 MALIGNANCY, BASICALLY THEY ARE 383 00:20:22,280 --> 00:20:23,600 LEUKEMIA. 384 00:20:23,600 --> 00:20:27,560 THESE 14 CENTRAL NERVOUS SYSTEM 385 00:20:27,560 --> 00:20:31,040 TUMORS, BASICALLY BRAIN TUMORS, 386 00:20:31,040 --> 00:20:34,240 10 GYNECOLOGICAL TUMORS, AND 8 387 00:20:34,240 --> 00:20:41,160 FIBROID TUMORS, EXCESS OF 388 00:20:41,160 --> 00:20:44,080 LEUKEMIA, CNS, GYNECOLOGIC AND 389 00:20:44,080 --> 00:20:49,440 FIBROID TUMORS COMPARED TO 390 00:20:49,440 --> 00:20:51,480 AMERICAN GENERAL POPULATION. 391 00:20:51,480 --> 00:20:57,640 LESS IN XP, WE DON'T KNOW WHY, 392 00:20:57,640 --> 00:21:00,320 ALSO LESS SYSTEM TUMORS IN XP 393 00:21:00,320 --> 00:21:02,440 COMPARED TO GENERAL POPULATION. 394 00:21:02,440 --> 00:21:10,280 SO NOT ALL ARE OVEREXPRESSED. 395 00:21:10,280 --> 00:21:13,840 IF WE PUT THE AGE OF THE TUMOR 396 00:21:13,840 --> 00:21:17,960 ON THE AGE OF DEATH OF THE 397 00:21:17,960 --> 00:21:22,360 PATIENT, MEDIAN AGE AT DIAGNOSIS 398 00:21:22,360 --> 00:21:25,960 IS 21 YEARS, AND DEATH 25 YEARS, 399 00:21:25,960 --> 00:21:32,560 SO FIRST TUMORS ARRIVE EARLY, 400 00:21:32,560 --> 00:21:34,080 AND THE TIME LIFE BETWEEN 401 00:21:34,080 --> 00:21:36,800 DIAGNOSIS AND THE DEATH OF THE 402 00:21:36,800 --> 00:21:40,120 PATIENT IS RELATIVELY SHORT, 403 00:21:40,120 --> 00:21:40,960 OKAY. 404 00:21:40,960 --> 00:21:47,000 SO IF WE PUT THE MEDIAN AGE AT 405 00:21:47,000 --> 00:21:47,760 DIAGNOSIS ACCORDING TO MUTATION 406 00:21:47,760 --> 00:21:54,440 TYPE YOU CAN SEE TWO TYPES, THE 407 00:21:54,440 --> 00:21:56,400 TUMOR HERE, MEDIAN AGE BETWEEN 408 00:21:56,400 --> 00:21:59,240 15 AND 25, SO THIS IS VERY, VERY 409 00:21:59,240 --> 00:22:00,360 EARLY. 410 00:22:00,360 --> 00:22:04,720 THIS IS BRAIN TUMOR, KIDNEY, 411 00:22:04,720 --> 00:22:09,000 HEAD AND NECK, THYROID, 412 00:22:09,000 --> 00:22:09,960 GYNECOLOGICAL TUMOR, AND 413 00:22:09,960 --> 00:22:11,360 HEMATOLOGICAL MALIGNANCY. 414 00:22:11,360 --> 00:22:19,760 WHY THREE TYPES OF TUMORS HERE, 415 00:22:19,760 --> 00:22:20,640 GASTROINTESTINAL, SYSTEM TUMORS, 416 00:22:20,640 --> 00:22:22,560 WHEREVER MAJOR DIAGNOSIS IS 417 00:22:22,560 --> 00:22:26,400 BETWEEN 50 AND 60, MORE OR LESS 418 00:22:26,400 --> 00:22:27,520 THE NORMAL AGE. 419 00:22:27,520 --> 00:22:33,360 HERE IN THE MIDDLE PATIENT WITH 420 00:22:33,360 --> 00:22:36,320 BREAST TUMORS, WE CANNOT DEDUCE 421 00:22:36,320 --> 00:22:36,560 ANYTHING. 422 00:22:36,560 --> 00:22:40,000 BUT INTERESTINGLY IF WE ASK THE 423 00:22:40,000 --> 00:22:42,000 QUESTION, WHICH KIND OF MUTATION 424 00:22:42,000 --> 00:22:44,440 GROUP ARE PRESENT IN THESE TWO 425 00:22:44,440 --> 00:22:47,800 TYPES OF TUMORS, PATIENT WITH 426 00:22:47,800 --> 00:22:53,400 TUMORS, WE CAN SAY THAT 90% OF 427 00:22:53,400 --> 00:22:58,120 THE PATIENTS, WITH EARLY BRAIN 428 00:22:58,120 --> 00:23:02,480 TUMORS ARE XPC PATIENT, 50% OF 429 00:23:02,480 --> 00:23:05,480 THESE PATIENT WITH LATE BRAIN 430 00:23:05,480 --> 00:23:10,600 TUMORS ARE XP VARIANT. 431 00:23:10,600 --> 00:23:13,560 SO XP VARIANTS LATE, XPC ARE 432 00:23:13,560 --> 00:23:19,760 EARLY BRAIN TUMORS. 433 00:23:19,760 --> 00:23:25,680 SO TO CALCULATE EXACTLY THE RISK 434 00:23:25,680 --> 00:23:26,880 FACTOR, THE XP PATIENT HAVE 435 00:23:26,880 --> 00:23:27,760 ALONG THEIR LIFE. 436 00:23:27,760 --> 00:23:31,240 IN ORDER TO CALCULATE THE RISK 437 00:23:31,240 --> 00:23:34,760 FACTOR, WE COULDN'T TAKE EACH OF 438 00:23:34,760 --> 00:23:38,480 THE XP PATIENT WHICH HAVE 439 00:23:38,480 --> 00:23:42,320 BEEN -- SOMETIME IN PUBLICATION 440 00:23:42,320 --> 00:23:44,040 THERE'S ONE PATIENT, NO IDEA 441 00:23:44,040 --> 00:23:46,360 ABOUT THE NUMBER OF PATIENTS 442 00:23:46,360 --> 00:23:49,840 WHICH ARE AROUND, NO IDEA ABOUT 443 00:23:49,840 --> 00:23:51,160 THEIR EPIDEMIOLOGY, SO WHAT WE 444 00:23:51,160 --> 00:23:56,960 DID IN FACT IS TO CALCULATE RISK 445 00:23:56,960 --> 00:24:02,960 FACTOR, BY TAKING INTO ACCOUNT 446 00:24:02,960 --> 00:24:05,160 FOUR INDEPENDENT SO THAT FOUR 447 00:24:05,160 --> 00:24:11,720 AMERICAN, FRENCH, BRAZILIAN AND 448 00:24:11,720 --> 00:24:14,240 ENGLISH, 434 XP PATIENT, WHICH 449 00:24:14,240 --> 00:24:17,880 REPRESENT NOW 50 TUMORS. 450 00:24:17,880 --> 00:24:19,200 SO OF COURSE 50 TUMORS WERE PART 451 00:24:19,200 --> 00:24:22,560 OF 89 TUMORS I JUST TALKED 452 00:24:22,560 --> 00:24:27,040 ABOUT, THESE TUMORS ARE PART OF 453 00:24:27,040 --> 00:24:29,560 COHORT WHERE WE KNOW THE 454 00:24:29,560 --> 00:24:30,000 FOLLOW-UP. 455 00:24:30,000 --> 00:24:35,360 PATIENT, WE KNOW THEIR AGE, THE 456 00:24:35,360 --> 00:24:39,640 EPIDEMIOLOGY AND SO ON AND SO 457 00:24:39,640 --> 00:24:41,080 FORTH. 458 00:24:41,080 --> 00:24:46,480 SO THE FIRST COHORT IS AMERICAN 459 00:24:46,480 --> 00:24:51,800 XP COHORT, NIH, 137 PATIENTS, 14 460 00:24:51,800 --> 00:24:52,440 INTERNAL TUMORS. 461 00:24:52,440 --> 00:24:59,880 I WANT TO THANK DR. KRAMER'S LAB 462 00:24:59,880 --> 00:25:02,080 THAT GAVE US UNPUBLISHED DATA, 463 00:25:02,080 --> 00:25:06,560 VERY USEFUL IN ORDER TO 464 00:25:06,560 --> 00:25:08,640 CALCULATE RISK FACTOR WITH 465 00:25:08,640 --> 00:25:11,720 BETTER EFFICACY. 466 00:25:11,720 --> 00:25:29,600 WE HAVE 176 FRENCH XP, 3 467 00:25:29,600 --> 00:25:32,000 BRAZILIAN PUBLISHED THIS YEAR, 468 00:25:32,000 --> 00:25:35,560 BY THE PROFESSOR AT THE 469 00:25:35,560 --> 00:25:38,320 UNIVERSITY OF SAN PAULO, 89 470 00:25:38,320 --> 00:25:55,720 ENGLISH XP PATIENT WITH TWO 471 00:25:55,720 --> 00:25:58,960 INTERNAL TUMORS, MAJORITY OF XP 472 00:25:58,960 --> 00:26:03,040 PATIENT ARE XPC, FOR THE ENGLISH 473 00:26:03,040 --> 00:26:06,160 AND AMERICAN COHORT THERE'S MORE 474 00:26:06,160 --> 00:26:09,800 XPA AND XPD THAN IN FRENCH AND 475 00:26:09,800 --> 00:26:12,680 BRAZILIAN COHORT, THAT MORE XPV 476 00:26:12,680 --> 00:26:14,760 IN BRAZILIAN AND FRENCH COHORT 477 00:26:14,760 --> 00:26:18,680 COMPARED TO THE AMERICAN ONE. 478 00:26:18,680 --> 00:26:21,560 SO, IF WE LOOK AT THE 479 00:26:21,560 --> 00:26:27,160 DISTRIBUTION OF THE TUMORS, IF 480 00:26:27,160 --> 00:26:39,320 WE LOOK AT 444 XP PATIENTS, 50% 481 00:26:39,320 --> 00:26:45,160 IN BLUE HERE, 12 XPA. 482 00:26:45,160 --> 00:27:01,800 WHEN YOU LOOK AT PERCENT, 0 XTA, 483 00:27:01,800 --> 00:27:11,120 6% APV, ONE AMERICAN PATIENT 484 00:27:11,120 --> 00:27:11,440 HERE. 485 00:27:11,440 --> 00:27:14,560 60% ARE THE MUTATION WHICH IS 486 00:27:14,560 --> 00:27:16,680 ORIGINALLY COMING FROM NORTH 487 00:27:16,680 --> 00:27:20,160 AFRICA. 488 00:27:20,160 --> 00:27:22,040 WE CAN CALCULATE THE HPC PATIENT 489 00:27:22,040 --> 00:27:25,640 HAS A HIGH RISK OF INTERNAL 490 00:27:25,640 --> 00:27:31,640 TUMORS, THE RATIO FOR XPC IS A 491 00:27:31,640 --> 00:27:34,080 FACTOR OF N COMPARED TO ALL THE 492 00:27:34,080 --> 00:27:35,600 MUTATION GROUPS SO XPC PATIENT 493 00:27:35,600 --> 00:27:38,840 ARE AT HIGH RISK OF INTERNAL 494 00:27:38,840 --> 00:29:10,200 TUMORS. 495 00:31:36,320 --> 00:31:40,040 ONE XPC SARCOMA, 16-YEAR-OLD 496 00:31:40,040 --> 00:32:00,200 GIRL WITH MUTATION FROM NIGERIA. 497 00:32:00,200 --> 00:32:10,840 THIS IS A GROUP, KNOWN FOR 498 00:32:10,840 --> 00:32:11,360 BIOINFORMATICS, TALENTED 499 00:32:11,360 --> 00:32:20,840 POSTDOC, AND I'M GOING TO SHOW 500 00:32:20,840 --> 00:32:29,200 YOU ESSENTIALLY THEIR WORK. 501 00:32:29,200 --> 00:32:50,720 HERE WE HAVE 6 XP-C LEUKEMIA. 502 00:32:50,720 --> 00:32:54,240 AS YOU CAN SEE COMPARED TO 503 00:32:54,240 --> 00:32:56,080 SPORADIC LEUKEMIA, 25-FOLD 504 00:32:56,080 --> 00:33:02,560 INCREASE IN SOMATIC MUTATION IN 505 00:33:02,560 --> 00:33:03,080 XPC LEUKEMIA. 506 00:33:03,080 --> 00:33:07,760 NOW YOU CAN COMPARE THE MUTATION 507 00:33:07,760 --> 00:33:09,760 PROFILE IN XP LEUKEMIA, XP 508 00:33:09,760 --> 00:33:13,440 TUMORS COMPARED TO SPORADIC 509 00:33:13,440 --> 00:33:18,480 CANCER, HERE IT'S BREAST CANCER, 510 00:33:18,480 --> 00:33:23,760 AND YOU SEE THE SIX POSSIBLE 511 00:33:23,760 --> 00:33:28,400 SUBSTITUTIONS. 512 00:33:28,400 --> 00:33:31,880 EACH BAR IS A PROPORTION OF 513 00:33:31,880 --> 00:33:33,200 MUTATION ACCORDING TO THE 514 00:33:33,200 --> 00:33:37,160 CLINICAL CONTEXT HERE, SO I'M 515 00:33:37,160 --> 00:33:42,560 SURE HERE THIS IS ACA, ACC, ACG, 516 00:33:42,560 --> 00:33:44,160 ACT, AND SO ON. 517 00:33:44,160 --> 00:33:52,960 SO, THIS IS THE MUTATION PROFILE 518 00:33:52,960 --> 00:33:57,080 WITH CORRESPONDING SPORADIC TYPE 519 00:33:57,080 --> 00:33:59,720 OF TUMOR. 520 00:33:59,720 --> 00:34:05,440 YOU CAN SEE THE MUTATION 521 00:34:05,440 --> 00:34:06,280 PROFILES ARE SIMILAR, WHICH 522 00:34:06,280 --> 00:34:09,240 MEANS HERE IT'S MORE OR LESS 523 00:34:09,240 --> 00:34:14,080 SPECIFIC OF THE XPC MINUS. 524 00:34:14,080 --> 00:34:17,680 THE MUTATION PROFILE IS 525 00:34:17,680 --> 00:34:19,480 PREDICTABLE, DIFFERENT FROM THE 526 00:34:19,480 --> 00:34:22,680 XPC ONE, PARTICULARLY THE 527 00:34:22,680 --> 00:34:29,880 MUTATION AT HIGHER SPORADIC 528 00:34:29,880 --> 00:34:35,360 COMPARED TO XPC ONE, HERE MORE 529 00:34:35,360 --> 00:34:35,600 SPORADIC. 530 00:34:35,600 --> 00:34:37,960 IF WE WANT TO COMPARE THE 531 00:34:37,960 --> 00:34:45,440 DIFFERENT PROFILES HERE, WE DO 532 00:34:45,440 --> 00:34:46,640 SCALING BETWEEN DIFFERENT 533 00:34:46,640 --> 00:34:51,480 PROFILE, YOU CAN SEE IN RED THIS 534 00:34:51,480 --> 00:34:56,760 IS THE XP MUTATION PROFILE, IN 535 00:34:56,760 --> 00:34:59,560 GRACE SPORADIC, YOU CAN SEE THAT 536 00:34:59,560 --> 00:35:03,640 MUTATIONAL PROFILE VERY FAR FROM 537 00:35:03,640 --> 00:35:07,280 EACH OTHER, 4% CORRESPONDS TO 538 00:35:07,280 --> 00:35:10,440 LEUKEMIA. 539 00:35:10,440 --> 00:35:12,080 SO I'M SURE YOU'VE SEEN THIS 540 00:35:12,080 --> 00:35:17,600 PICTURE A LOT IN THE PAST, THIS 541 00:35:17,600 --> 00:35:20,040 IS THE WORK OF ALEXANDER 542 00:35:20,040 --> 00:35:23,880 PUBLISHED SOMETIME IN THE PAST. 543 00:35:23,880 --> 00:35:32,680 IN FACT, WHAT HE HAS DONE IS 544 00:35:32,680 --> 00:35:33,880 TAKE THOUSANDS OF CANCERS, 545 00:35:33,880 --> 00:35:38,480 EXTRACT FOR MUTATIONAL PROFILE 546 00:35:38,480 --> 00:35:41,680 OF CANCER, TRIED TO EXTRACT 547 00:35:41,680 --> 00:35:43,520 SEVERAL MUTATIONAL SIGNATURE, IN 548 00:35:43,520 --> 00:35:48,880 ORDER TO UNDERSTAND HOW 549 00:35:48,880 --> 00:35:51,280 MUTATIONAL PROFILE HAS BEEN BEEN 550 00:35:51,280 --> 00:35:53,120 FORMED, WHERE IT'S COMING FROM. 551 00:35:53,120 --> 00:35:59,080 IN FACT, SOME OF THE SIGNATURE 552 00:35:59,080 --> 00:36:02,800 HERE CORRESPONDS TO GIVEN 553 00:36:02,800 --> 00:36:04,560 ETIOLOGY, FOR EXAMPLE SMOKING, 554 00:36:04,560 --> 00:36:08,480 UV LIGHT, HE CAN RECOGNIZE THE 555 00:36:08,480 --> 00:36:12,760 MUTATION WE FOUND ALSO IN SKIN 556 00:36:12,760 --> 00:37:43,760 CANCER OF XP PATIENTS.