Recurrent deletions at 6q in early age of onset non-HNPCC- and non-FAP-associated intestinal carcinomas. Evidence for a novel cancer susceptibility locus at 6q14-q22.
Hereditary intestinal cancers mainly occur in the framework of the familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) syndromes. However, in about 50% of young patients with intestinal cancer clinically suspicious of an inherited cancer predisposition, no underlying molecular alteration can be identified. To determine the genetic profile of early onset intestinal cancer in the absence of a known cancer predisposition, we have analyzed 12 small and large intestinal tumors from 11 non-FAP, non-HNPCC, and noninflammatory bowel disease patients diagnosed under the age of 35years using a combination of comparative genomic hybridization and loss of heterozygosity (LOH) analysis. The distribution of chromosomal gains and deletions was similar to late onset carcinomas except for 6q alterations which were found in 50% of carcinomas. To define a shared region affected by allelic imbalance, detailed LOH analysis at chromosome 6 was performed on three carcinomas from two patients which showed small interstitial 6q deletions. A minimal area of deletion overlap between markers D6S1652 and D6S1657 (6q14-22) was identified. In a patient with small and large intestinal carcinoma and seven adenomas, loss of identical parental 6q14-22 alleles was seen in both carcinomas and in three of the adenomas. Our data indicate that alterations affecting 6q are frequent in early onset intestinal carcinomas. Moreover, deletions of identical parental alleles in a 35 Mbp area at 6q in multiple independent tumors from one of the patients are compatible with the existence of a novel 6q-associated cancer susceptibility syndrome.
Bläker
Hendrik
H
Department of Pathology, University of Heidelberg, Heidelberg, Germany. hendrik_blaeker@med.uni-heidelberg.de
Mechtersheimer
Gunhild
G
Sutter
Christian
C
Hertkorn
Christian
C
Kern
Michael A
MA
Rieker
Ralf J
RJ
Penzel
Roland
R
Schirmacher
Peter
P
Kloor
Matthias
M
D011125:Adenomatous Polyposis Coli / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D014408:Biomarkers, Tumor / Q000235:genetics*; D002872:Chromosome Deletion; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D053842:Microsatellite Instability
D014408:Biomarkers, Tumor