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Surgery and Anesthesia 2018 & Euro Gastro Congress 2018 Case Reports in Surgery and Invasive Procedures| Volume 2
&
GASTROENTEROLOGY
3rd International Conference on
SURGERY AND ANESTHESIA
International Conference on
Joint Event on
OF EXCELLENCE
IN INTERNATIONAL
MEETINGS
YEARS
Manuel Perucho, Case Rep Surg Invasive Proced 2018, Volume 2
THE GENETICS-EPIGENETICS
CHRONOLOGIES AND HIERARCHIES IN
COLON CANCER
T he cancer cell genome accumulates numerous genetic and epigenetic al-
terations. We showed that a subset of colon cancers (CC) display amutator
phenotype because they harbor hundreds of thousand of somatic mutations
simple repeats or microsatellites. Microsatellite instability (MSI) is diagnostic
of a distinct molecular pathway for CC as these tumors are very different in
genotype and phenotype compared with those without MSI. MSI has become
a robust and widely used marker with applications in diagnosis and prognosis
of hereditary and non-hereditary CC. Increased DNA hyper methylation was
postulated to be the result of a CpG Island methylator phenotype (“CIMP”) and
underlies the tumorigenesis of some colon cancers when the mismatch repair
gene MLH1 is silenced, causing MSI. We showed that the genetic alterations
(MSI) supersede the previous epigenetic alterations (“CIMP”) in tumor pheno-
type in colon cancer. The same conclusion is reached when using the recent
data from the cancer Genome Atlas (TCGA) consortium. Among the genes
frequently hyper methylated are the ADAMTS, encoding extracellular matrix
metallopeptidases. Epigenetic silencing of ADAMTS genes in CC takes place
in a coordinated manner, not only in cis (linearly linked), but also in trans (in
different chromosomes). This is not due to “CIMP” because does not associ-
ate with right colon and BRAF mutations, and few of the ADAMTS genes are
polycomb repressor complex (PRC) targets, landmarks of the CIMP tumors.
We also showed that both hyper methylation and hypo methylation of DNA
increase with age of colon cancer (CC) patients. In addition, we showed that
hypo methylation (in contrast with hyper methylation) correlates with genomic
damage and, in turn, represents a survival biomarker in patients: the greater
the hypo methylation the worse the survival, both in gastric cancer and CC.
This allowed us to propose a “wear and tear” hypothesis linking aging, gradual
demethylation of the genome, genomic instability, and gastrointestinal cancer.
Biography
Manuel Perucho University of Madrid, held facul-
ty appointments at State University of New York
(SUNY) Stony Brook. From 1995-2009 was profes-
sor and program director, Sanford-Burnham-Pre-
bys Medical Discovery Institute (SBP) La Jolla,
California, where he holds an adjunct professor
appointment. He was director of the Institute of
predictive & personalized medicine of cancer (IMP-
PC) (2009-2016), and currently is director, program
of predictive & personalized medicine of cancer
(PMPPC), Institute Germans Trias I Pujol (IGTP),
Barcelona, Spain. He was awarded an AACR pro-
fessorship in basic cancer research, serves in
editorial boards of several journals, and reviewed
research grants of many agencies and hundreds of
papers of over 60 journals.
Manuel Perucho
Institute Germans Trias I Pujol (IGTP), Spain