>>WELCOME TO THE DNA REPAIR
INTEREST GROUP CONFERENCE
DR. SARASIN, THIS IS ACTUALLY
HIS SECOND PRESENTATION TO OUR
GROUP, THE FIRST WAS IN 2003.
AND YOU CAN ACTUALLY SEE WHAT HE
LOOKED LIKE THEN, AND WHAT I
LOOKED LIKE THEN.
[LAUGHTER]
SEVENTEEN YEARS AGO, HE WAS
TALKING ABOUT XP VARIANT, HOW HE
WAS GOING TO CURE XPC AT THAT
POINT.
WE GO BACK A LITTLE BIT.
HE IS EMERITUS RESEARCH
DIRECTOR, IN FRANCE, ALSO
DIRECTOR OF LABORATORY OF
DIAGNOSIS DNA REPAIR DISEASES,
AND FROM HIS OFFICE YOU COULD
SEE THE EIFFEL TOWER.
HE WAS ORIGINALLY FROM -- HE GOT
HIS Ph.D. DEGREE, UNIVERSITY
OF PARIS, STUDYING BACTERIA, HE
WORKED -- CONTINUED WITH
(INDISCERNIBLE), SOS PATHWAY,
INTERNATIONAL SCIENTIST, WHO
WENT TO STANFORD AND AFLOTOXIN
TO XERODERM, MOVED SOUTH TO RIO
DE JANEIRO, BRAZIL, VISITING
PROFESSOR, A MEMBER OF MANY
ORGANIZATIONS.
HE WAS IN THE (INDISCERNIBLE)
FOR THE EUROPEAN SPACE AGENCY,
THINGS HE DOES ALL OVER SPACE,
INTERNATIONAL ASSOCIATION OF
ENVIRONMENTAL MUTAGENESIS AND
STUDIES CHAIRMAN OF SCIENTIFIC
COUNCIL FOR CANCER AND HIS MAIN
INTERESTS ARE DIAGNOSIS OF
REPAIR DEFICIENCY DISEASES, AND
OTHERS, HE HAS A NUMBER OF
FIRSTS IN DIAGNOSING, INCLUDING
PRENATAL DIAGNOSIS, AND
(INDISCERNIBLE) FOR MANY YEARS,
SO TODAY HE WILL BE TALKING
ABOUT NOT ONLY THE SKIN CANCER,
XERODERMA AROUND THE WORLD, NEW
STUDIES OF INTERNAL CANCERS AND
NOW WE'LL HAVE A FEW WORDS.
>> TO ADD TO THAT
INTRODUCTION, I HAVE
KNOWN ALAIN SINCE DAYS AT
STANFORD AND REALLY TREMENDOUSLY
ENJOYED YOUR WORK AND MEETING
YOU ON MANY OCCASIONS, AND YOU
HAVE MADE GREAT STRIDES IN THE
XP AND RELATED FIELDS AND VERY
BROAD-BASED, IT'S A PLEASURE TO
HAVE YOU HERE, AND THEN I JUST
WANTED TO MENTION THAT WE HAVE
QUESTIONS, IF ANY OF THE PEOPLE
ATTENDING WOULD LIKE TO ASK A
QUESTION PLEASE TYPE IT ON THE
CHAT BOX AND KEN AND I WILL READ
THEM UP FOR ALAIN AND YOU, AFTER
THE TALK.
THANK YOU VERY MUCH.
>> OKAY.
TAKE IT AWAY, ALAIN.
>>THANK YOU FOR THE INVITATION
TO COME TO WASHINGTON, BUT
UNFORTUNATELY I'M STILL IN PARIS
BECAUSE OF THE COVID, OF COURSE.
YOU TOLD ME, YOU SAID THAT FROM
MY OFFICE I CAN SEE THE EIFFEL
TOWER, WHICH IS STILL TRUE, AND
I SHOWED YOU A PICTURE THAT I
CANNOT SEE FROM MY OFFICE, WHICH
IS A PICTURE OF ONE OF THE
ISLANDS I'M GOING TO TALK ABOUT
IN A MINUTE, WHICH IS CALLED
(INDISCERNIBLE).
SO I'M GOING TO OF COURSE AS YOU
MIGHT EXPECT TALK ABOUT XPs
AND NUCLEOTIDE REPAIR.
SINCE DR. KRAMER ASKED ME TO
EXPLAIN A LITTLE BIT SOME
AFRICAN COUNTRY AND FROM BRAZIL
SO I WILL GIVE YOU AN EXAMPLE
HOW WE CAN DO HISTORY AND
GEOGRAPHY AND BRING GENE
MUTATION ANALYSIS AT THE SAME
TIME.
THEN I WILL SWITCH TO MY MAIN
TOPIC, RISK FACTOR OF DEVELOPING
INTERNAL TUMORS IN XP PATIENTS,
AND WHAT IS A MUTATIONAL
LANDSCAPE OF A METALLURGY
MALIGNANCY, MUCH MORE COMMON IN
NORTH AFRICA, JAPAN, PAKISTAN,
RARE IN EUROPE.
THE PATIENTS ARE UV SENSITIVE
AND THEY GET SKIN DISORDER, THIS
IS DUE TO THE FACT THEY HAVE
DEFICIENCY IN GENE REPAIR IN
NUCLEOTIDE REPAIR, MUTATION IN
ONE OF THE SEVEN XP GENES OR DUE
TO MUTATION IN THE POLYMERASE,
XP VARIANT.
IF THESE PATIENTS ARE NOT FULLY
PROTECTED FROM SUN EXPOSURE,
THEY WILL DEVELOP VERY HIGH
FREQUENCY OF UV-INDUCED SKIN
CANCER, UNFORTUNATELY WILL HAVE
A SHORT LIFETIME ALSO.
SO, WHAT ABOUT MY RELATIONSHIP
WITH AFRICA AND BRAZIL?
I WILL START HERE WITH THE
COMORES, THE WHOLE ISLAND WHICH
FORMED THE COMORIAN ARCHIPELAGO,
THESE ISLANDS ARE LOCATED IN
BETWEEN THE EAST AFRICAN COAST,
YOU CAN RECOGNIZE HERE
MOZAMBIQUE, KENYA, AND HERE WE
SEE THE BIG ISLAND OF
MADAGASCAR.
INTERESTINGLY, THE EQUATOR IS
VERY, VERY CLOSE TO THESE
ISLANDS, WHICH IS VERY BAD NEWS
FOR XP PATIENTS.
SO, I'VE BEEN THERE BECAUSE
THESE WHOLE ISLANDS WERE FRENCH
40 YEARS AGO.
NOW IT'S A FREE WHITE ISLAND,
AND THE YELLOW ONE, THIS IS THE
FIRST PICTURE I SHOWED YOU, A
FRENCH DEPARTMENT.
AND XP PATIENTS HAVE BEEN
REPORTED IN SOME OF THE ISLANDS,
SO I WENT THERE AND I ANALYZED,
I DID SOME CLASSICAL ANALYSIS OF
XP PATIENTS, WE FOUND IN THIS
ISLAND PROBABLY ONE OF THE
HIGHEST INCIDENCE OF XP, 1 IN
5,000, THE MUTATION, EXOME 12,
AT THE TIME WE PUBLISHED THIS,
THE COMORIAN MUTATION, THE
MUTATION WAS NOT DISCOVERED
EVERYWHERE ELSE IN THE WORLD.
WE CALCULATE THE AGE OF MUTATION
INSIDE THE ISLAND, IF WE BELIEVE
THE ISLAND IS CLOSE BUBBLE, WE
CALCULATE THE AGE TO BE 800
YEARS OLD.
WE'LL COME BACK TO THAT.
HIGH INCIDENCE OF XPs IS
ESSENTIALLY DUE TO THE CLOSE
ENVIRONMENT OF THE ISLAND, ALSO
TO THE FACT THAT THE PEOPLE HAVE
A REMARKABLE DEGREE OF
INBREEDING, STILL POLYGAMY IN
SOME ISLANDS HERE.
THESE PATIENTS ARE BLACK SKINNED
PATIENTS, I FOUND THIS GUY MORE
THAN TEN YEARS AGO, NOW BACK IN
PARIS, AND THIS IS THE SAME GUY,
AT 7 YEARS DIFFERENCE, YOU CAN
RECOGNIZE THE XP DISEASE IS HIGH
MUTATION DISEASE, INCREASE
MUTATION IN 7 YEARS BUT HIGH
MUTATION IN BLACK SKIN, IN FACT
XP IS BOTH (INDISCERNIBLE)
DISEASE.
USUALLY BLACK PEOPLE ARE
RELATIVELY PROTECTED FROM SKIN
CANCER BUT STILL XP PATIENTS
HAVE SKIN CANCER, PARTICULARLY
IN THE TOP OF THE HEAD HERE, AND
INTERESTINGLY THEY DEVELOP
TUMORS ON THE TIP OF THE TONGUE
AS WELL, BECAUSE THE TONGUE IS
NOT EXPOSED -- IS EXPOSED TO
SUN, AND IS NOT PROTECTED BY
MELANIN.
MOST OF THE PATIENTS GET ON THE
TIP OF THE TONGUE.
AND UNFORTUNATELY, THESE
PATIENTS DON'T PROTECT THEIR
EYES, ALTHOUGH WE BRING THEM
SUNGLASSES EVERY YEAR, OR MOST,
AND SO USUALLY THEY BECOME BLIND
BEFORE -- BETWEEN THE AGE OF 10
OR 15.
SO, WE THOUGHT THE MUTATION WAS
SPECIFIC OF COMORES, A COUPLE
YEARS AGO THE GROUP OF DR.
KUKURU IN PRETORIA, HERE, THE
RED POINT HERE, IN SOUTH AFRICA,
ALSO IN ZIMBABWE, WHICH IS HERE,
IN KENYA WE FOUND A PATIENT, IN
MOZAMBIQUE WE FOUND PATIENT,
ANALYZED, THE PATIENT IN EAST
AFRICA HAVE XPC MUTATION OF
COMORES.
WHEN WE CALCULATE AGE OF
MUTATION, AGE OF MUTATION WAS
ABOUT 1100 YEARS, WHICH MEANS
MUTATION IN EAST AFRICA WAS
OLDER THAN THE MUTATION IN
COMORES, INDEED WHEN WE LOOK AT
HISTORY OF COMORES, THE ISLANDS
WHERE PEOPLE BY EAST
AFRICAN-BORN POPULATION AROUND
THE 7th AND 10th CENTURY,
AND SHOULD HAVE BEEN PEOPLE BY
SOME XP HETEROZYGOTE, GIVE RISE
TO HIGH XP DUE TO ISLAND
ISOLATION.
A FEW YEARS AGO THE PAPER WAS
PUBLISHED, LAST YEAR DR. WALID
IN PAKISTAN REPORTED A GROUP OF
XP PATIENTS, THESE PATIENTS HAVE
COMORIAN MUTATION.
HERE AGAIN EAST AFRICAN COAST,
AND SO GEOGRAPHY IS STILL THE
SAME SO HERE YOU HAVE THE EAST
AFRICAN COUNTRY, AND HERE YOU
HAVE THE ARABIC HERE, AND HERE
YOU HAVE SOUTH IRAN, AND THE
PLACE WHICH AT THAT TIME WAS
VERY -- THE CAPITAL OF IRAN,
WHAT IS IRAN NOW.
IN FACT BETWEEN 11th AND
13th CENTURY, THIS IS HISTORY,
THE ARABS WERE DOWN BY BOAT FROM
THIS ARABIC COUNTRY TO SOUTH
ALONG THE EAST COAST OF AFRICA.
AND THEY WERE SAILORS, TRADERS,
DOING BUSINESS WITH THE
DIFFERENT EAST AFRICAN COUNTRY,
AT THE SAME TIME WHEN THEY WENT
BACK HOME THEY WENT BY TAKING
THE BLACK PEOPLE AS SLAVES,
BLACK MEN AS SLAVE, TAKING BLACK
WOMEN AS SPOUSE, OKAY?
SO A LOT OF BLACK PEOPLE FROM
THE EAST COAST COUNTRY AS WELL
AS SOME ISLAND LIKE ZANZIBAR
WHICH IS HERE THE BLACK WENT
BACK TO SOUTH IRAN AND THESE
PATIENTS WERE BEING DESCRIBED TO
HAVE COMORIAN MUTATION, ALSO
HAPLOTYPE THAT WE CAN FIND IN
EAST AFRICA.
SO WHAT WE BELIEVE IS THAT THE
BLACK PEOPLE WERE TAKEN AS SLAVE
HERE, NOW LIVING THERE.
AND INTERESTINGLY THE XP FROM
PAKISTAN ARE LIVING AS NOMAD
TRIBES, AND THEY ARE LIVING IN
BETWEEN SOUTH IRAN AND PAKISTAN
ACCORDING TO THE TIME OF YEAR.
AND FINALLY, TO MAKE A LONG
STORY SHORT, I JUST WANTS TO
REMIND YOU THAT THERE WAS A
SEA-GOING SLAVE TRADE BETWEEN
THE WEST COAST OF AFRICA AND THE
SOUTH AMERICA AND CENTRAL
AMERICA AND NORTH AMERICA, AND
WHEN THE SLAVE TRADE WAS
FORBIDDEN ALONG THE COAST, THE
WEST COAST, THEN THE PEOPLE WENT
FROM THE EAST COAST COUNTRIES
AND AT THAT TIME MOZAMBIQUE
WHICH HERE, MOZAMBIQUE WAS
PORTUGUESE, SO THERE WAS SLAVE
TRADE BETWEEN MOZAMBIQUE, IT'S
BEEN CALCULATED THAT ABOUT 20%
OF BLACK AFRICAN SLAVE IN BRAZIL
CAME FROM EAST AFRICA, AND WHEN
THESE PEOPLE CAME FROM EAST
AFRICA TO RIO DE JANEIRO, FROM
THE COAST COMING FROM
MOZAMBIQUE.
WITH THE GROUP OF
[SPEAKING FRENCH] AS NATIONAL
INSTITUTE OF SAO PAULO, THE
PROFESSOR AND DOCTOR IN MY LAB
FROM UNIVERSITY OF SAN PAOLO,
THEY LOCATED IN BRAZIL THE XPC
PATIENT WITH COMORIAN MUTATION.
MOST OF XP PATIENT ARE LOCATED
HERE CLOSE TO RIO DE JANEIRO
HARBOR, CLOSE TO SALVADORE, IN
THE NORTHEAST OF BRAZIL, CLOSE
TO RECIFE.
SO WHAT I CALL THE AFRICAN XP
MUTATION IS PROBABLY A MUTATION
WHAT I CALL COMORIAN, WE SHOULD
CALL IT XPC, 1100 YEARS AGO.
THEN IT CAME FROM COMORES BY
EAST AFRICAN PEOPLE WHICH WERE
SOME OF THEM WERE HETEROZYGOUS.
DURING THE ARABS, SOME BLACK
PEOPLE WENT TO SOUTH IRAN, NOW
LOCATED BETWEEN SOUTH IRAN,
PAKISTAN, AND FINALLY TO A FEW
CENTURIES AAGO DUE TO SLAVE
TRADING WENT TO BRAZIL.
TO ANSWER THE QUESTION, THIS IS
ONE OF MY RELATIONSHIPS WITH
BRAZIL, IT'S ONE OF THE
IMPORTANT ONE.
SO NOW WE SWITCH GEAR AND TALK
ABOUT AFRICAN XP, VERY IMPORTANT
SUBJECT FOR THE XP PATIENT NOW.
XP PATIENTS NOW LIVE LONGER IN
DEVELOPING COUNTRIES BECAUSE
THEY ARE VERY WELL EDUCATED IN
TERMS OF UNDERSTANDING THEIR
DISEASE AND UNDERSTANDING WHAT
THEY SHOULD DO TO BE WITH SUN
EXPOSURE, AND ALSO MEDICAL
DOCTOR AND FAMILIES ARE BETTER
EDUCATED.
AS I'M GOING TO SHOW YOU AT THE
END, AT LEAST IN FRANCE, BUT
IT'S TRUE NOW IN SOME OTHER
COUNTRY, WE HAVE DEVELOPED
PROTECTION WHICH CAN PROTECT
ALMOST TO 100% WHEN THESE
PATIENTS GET OUTSIDE.
XP PATIENTS ARE DEFICIENT, SO
THE SKIN CELLS GIVE RISE TO SKIN
CANCER, AND WHAT ABOUT INTERNAL
ORGANS?
SO, SOME REPORT HAVE BEEN
PUBLISHED IN THE PAST,
PARTICULARLY DR. KRAMER'S LAB,
REPORTED 10 TO 20 HIGHER RISK OF
BRAIN TUMORS IN XP, AND RECENTLY
WE PUBLISHED PAPER LAST YEAR,
REPORTED 13 XPC PATIENT WITH
LEUKEMIA, AND DR. KRAMER'S LAB
REPORTED THIS YEAR FOUR XPC
PATIENT, AMERICAN XPC PATIENT
WITH LEUKEMIA AS WELL.
SO, WHAT I'VE DONE, TO COLLATE
PUBLISHED IN THE LITERATURE
BETWEEN 1958 AND NOW.
WHY 1958?
BECAUSE THIS IS THE FIRST REPORT
WHEN XP PATIENT WITH LEUKEMIA
AND BY DOING THAT I COLLATEN 89
XP INTERNATIONALS CORRESPONDING
TO 88 XP PATIENTS.
THESE PATIENTS RECEIVED
(INDISCERNIBLE) EARLIER, ALMOST
50% OF XP ARE ORIGINATED FROM
NORTH AFRICA, ALMOST ALL OF THEM
ARE LIVING IN FRANCE, FRENCH,
THEY LIVE IN FRANCE, OR THEY
LIVE IN THE STATES, OR SOME IN
BRAZIL.
20% ARE FROM THE STATES.
8% FROM JAPAN.
WHEN KNOWN, WE DON'T HAVE
COMPLEMENTATION, IN 1958 YOU CAN
IMAGINE THE COMPLEMENTATION
GROUP WERE NOT KNOWN, BUT WHEN
WE KNOW THE COMPLEMENTATION
GROUP 83%, THE VAST MAJORITY ARE
XPC, THE VAST MAJORITY
ORIGINATESSED FROM NORTH AFRICA,
FOUND THE MUTATION, WHICH IS
DELETION OF TG, IN THE EXOME,
NORTH AFRICAN MUTATION.
IF WE LOOK AT THE FREQUENCY OF
THE TUMOR, XP PATIENTS, YOU CAN
SEE THAT 30 INTERNATIONALS IN XP
WHICH ARE HEMATOLOGICAL
MALIGNANCY, BASICALLY THEY ARE
LEUKEMIA.
THESE 14 CENTRAL NERVOUS SYSTEM
TUMORS, BASICALLY BRAIN TUMORS,
10 GYNECOLOGICAL TUMORS, AND 8
FIBROID TUMORS, EXCESS OF
LEUKEMIA, CNS, GYNECOLOGIC AND
FIBROID TUMORS COMPARED TO
AMERICAN GENERAL POPULATION.
LESS IN XP, WE DON'T KNOW WHY,
ALSO LESS SYSTEM TUMORS IN XP
COMPARED TO GENERAL POPULATION.
SO NOT ALL ARE OVEREXPRESSED.
IF WE PUT THE AGE OF THE TUMOR
ON THE AGE OF DEATH OF THE
PATIENT, MEDIAN AGE AT DIAGNOSIS
IS 21 YEARS, AND DEATH 25 YEARS,
SO FIRST TUMORS ARRIVE EARLY,
AND THE TIME LIFE BETWEEN
DIAGNOSIS AND THE DEATH OF THE
PATIENT IS RELATIVELY SHORT,
OKAY.
SO IF WE PUT THE MEDIAN AGE AT
DIAGNOSIS ACCORDING TO MUTATION
TYPE YOU CAN SEE TWO TYPES, THE
TUMOR HERE, MEDIAN AGE BETWEEN
15 AND 25, SO THIS IS VERY, VERY
EARLY.
THIS IS BRAIN TUMOR, KIDNEY,
HEAD AND NECK, THYROID,
GYNECOLOGICAL TUMOR, AND
HEMATOLOGICAL MALIGNANCY.
WHY THREE TYPES OF TUMORS HERE,
GASTROINTESTINAL, SYSTEM TUMORS,
WHEREVER MAJOR DIAGNOSIS IS
BETWEEN 50 AND 60, MORE OR LESS
THE NORMAL AGE.
HERE IN THE MIDDLE PATIENT WITH
BREAST TUMORS, WE CANNOT DEDUCE
ANYTHING.
BUT INTERESTINGLY IF WE ASK THE
QUESTION, WHICH KIND OF MUTATION
GROUP ARE PRESENT IN THESE TWO
TYPES OF TUMORS, PATIENT WITH
TUMORS, WE CAN SAY THAT 90% OF
THE PATIENTS, WITH EARLY BRAIN
TUMORS ARE XPC PATIENT, 50% OF
THESE PATIENT WITH LATE BRAIN
TUMORS ARE XP VARIANT.
SO XP VARIANTS LATE, XPC ARE
EARLY BRAIN TUMORS.
SO TO CALCULATE EXACTLY THE RISK
FACTOR, THE XP PATIENT HAVE
ALONG THEIR LIFE.
IN ORDER TO CALCULATE THE RISK
FACTOR, WE COULDN'T TAKE EACH OF
THE XP PATIENT WHICH HAVE
BEEN -- SOMETIME IN PUBLICATION
THERE'S ONE PATIENT, NO IDEA
ABOUT THE NUMBER OF PATIENTS
WHICH ARE AROUND, NO IDEA ABOUT
THEIR EPIDEMIOLOGY, SO WHAT WE
DID IN FACT IS TO CALCULATE RISK
FACTOR, BY TAKING INTO ACCOUNT
FOUR INDEPENDENT SO THAT FOUR
AMERICAN, FRENCH, BRAZILIAN AND
ENGLISH, 434 XP PATIENT, WHICH
REPRESENT NOW 50 TUMORS.
SO OF COURSE 50 TUMORS WERE PART
OF 89 TUMORS I JUST TALKED
ABOUT, THESE TUMORS ARE PART OF
COHORT WHERE WE KNOW THE
FOLLOW-UP.
PATIENT, WE KNOW THEIR AGE, THE
EPIDEMIOLOGY AND SO ON AND SO
FORTH.
SO THE FIRST COHORT IS AMERICAN
XP COHORT, NIH, 137 PATIENTS, 14
INTERNAL TUMORS.
I WANT TO THANK DR. KRAMER'S LAB
THAT GAVE US UNPUBLISHED DATA,
VERY USEFUL IN ORDER TO
CALCULATE RISK FACTOR WITH
BETTER EFFICACY.
WE HAVE 176 FRENCH XP, 3
BRAZILIAN PUBLISHED THIS YEAR,
BY THE PROFESSOR AT THE
UNIVERSITY OF SAN PAULO, 89
ENGLISH XP PATIENT WITH TWO
INTERNAL TUMORS, MAJORITY OF XP
PATIENT ARE XPC, FOR THE ENGLISH
AND AMERICAN COHORT THERE'S MORE
XPA AND XPD THAN IN FRENCH AND
BRAZILIAN COHORT, THAT MORE XPV
IN BRAZILIAN AND FRENCH COHORT
COMPARED TO THE AMERICAN ONE.
SO, IF WE LOOK AT THE
DISTRIBUTION OF THE TUMORS, IF
WE LOOK AT 444 XP PATIENTS, 50%
IN BLUE HERE, 12 XPA.
WHEN YOU LOOK AT PERCENT, 0 XTA,
6% APV, ONE AMERICAN PATIENT
HERE.
60% ARE THE MUTATION WHICH IS
ORIGINALLY COMING FROM NORTH
AFRICA.
WE CAN CALCULATE THE HPC PATIENT
HAS A HIGH RISK OF INTERNAL
TUMORS, THE RATIO FOR XPC IS A
FACTOR OF N COMPARED TO ALL THE
MUTATION GROUPS SO XPC PATIENT
ARE AT HIGH RISK OF INTERNAL
TUMORS.
ONE XPC SARCOMA, 16-YEAR-OLD
GIRL WITH MUTATION FROM NIGERIA.
THIS IS A GROUP, KNOWN FOR
BIOINFORMATICS, TALENTED
POSTDOC, AND I'M GOING TO SHOW
YOU ESSENTIALLY THEIR WORK.
HERE WE HAVE 6 XP-C LEUKEMIA.
AS YOU CAN SEE COMPARED TO
SPORADIC LEUKEMIA, 25-FOLD
INCREASE IN SOMATIC MUTATION IN
XPC LEUKEMIA.
NOW YOU CAN COMPARE THE MUTATION
PROFILE IN XP LEUKEMIA, XP
TUMORS COMPARED TO SPORADIC
CANCER, HERE IT'S BREAST CANCER,
AND YOU SEE THE SIX POSSIBLE
SUBSTITUTIONS.
EACH BAR IS A PROPORTION OF
MUTATION ACCORDING TO THE
CLINICAL CONTEXT HERE, SO I'M
SURE HERE THIS IS ACA, ACC, ACG,
ACT, AND SO ON.
SO, THIS IS THE MUTATION PROFILE
WITH CORRESPONDING SPORADIC TYPE
OF TUMOR.
YOU CAN SEE THE MUTATION
PROFILES ARE SIMILAR, WHICH
MEANS HERE IT'S MORE OR LESS
SPECIFIC OF THE XPC MINUS.
THE MUTATION PROFILE IS
PREDICTABLE, DIFFERENT FROM THE
XPC ONE, PARTICULARLY THE
MUTATION AT HIGHER SPORADIC
COMPARED TO XPC ONE, HERE MORE
SPORADIC.
IF WE WANT TO COMPARE THE
DIFFERENT PROFILES HERE, WE DO
SCALING BETWEEN DIFFERENT
PROFILE, YOU CAN SEE IN RED THIS
IS THE XP MUTATION PROFILE, IN
GRACE SPORADIC, YOU CAN SEE THAT
MUTATIONAL PROFILE VERY FAR FROM
EACH OTHER, 4% CORRESPONDS TO
LEUKEMIA.
SO I'M SURE YOU'VE SEEN THIS
PICTURE A LOT IN THE PAST, THIS
IS THE WORK OF ALEXANDER
PUBLISHED SOMETIME IN THE PAST.
IN FACT, WHAT HE HAS DONE IS
TAKE THOUSANDS OF CANCERS,
EXTRACT FOR MUTATIONAL PROFILE
OF CANCER, TRIED TO EXTRACT
SEVERAL MUTATIONAL SIGNATURE, IN
ORDER TO UNDERSTAND HOW
MUTATIONAL PROFILE HAS BEEN BEEN
FORMED, WHERE IT'S COMING FROM.
IN FACT, SOME OF THE SIGNATURE
HERE CORRESPONDS TO GIVEN
ETIOLOGY, FOR EXAMPLE SMOKING,
UV LIGHT, HE CAN RECOGNIZE THE
MUTATION WE FOUND ALSO IN SKIN
CANCER OF XP PATIENTS.