High frequency of chromosome 14 deletion in early-onset colon cancer.
OBJECTIVE
Several genes have been recognized, when mutated in the germline, to highly predispose to colorectal cancer, impairing the DNA mismatch repair system in hereditary nonpolyposis colon cancer syndrome, or APC/MYH in adenomatous polyposis. However, 10 percent of microsatellite stable colorectal cancer is reported to develop in an unexplained context of genetic predisposition. This study was designed to depict the genetic mechanisms underlying early-onset microsatellite stable colon cancers.


METHODS
Patients younger than aged 50 years undergoing primary surgical resection for colon carcinoma were collected prospectively between 1993 and 2003. A first series of 8 samples has been allelotyped using 361 poly-CA polymorphisms distributed on the 39 autosomal arms within a larger set of 166 sporadic tumors. Genotyping of 24 poly-CA polymorphisms distributed on the 8 chromosomes exhibiting allelic losses in more than 30 percent of the previous cases was then applied to an independent series of 40 tumors. A third series of 70 tumors has been genotyped on chromosome 14 only.


RESULTS
Comparison of genomic profile from patients younger and older than aged 50 years at the 8 most frequently lost chromosomes allowed, identify chromosome 14 as showing a significant difference between the two groups. Dense chromosome 14 genotyping detected two partial deletions in a general background of 57 percent allelic loss, pointing at a region located between D14S63 and D14S292.


CONCLUSIONS
These observations suggest that a tumor-suppressor gene located on chromosome 14 might have an important role in microsatellite stable colon carcinogenesis. Because it seems to be more frequently involved in early-onset cases, it could be a good candidate in inherited conditions.
Mourra
Najat
N
Department of Pathology, Saint-Antoine Hospital, Paris, France.
Zeitoun
Guy
G
Buecher
Bruno
B
Finetti
Pascal
P
Lagarde
Arnaud
A
Adelaide
José
J
Birnbaum
Daniel
D
Thomas
Gilles
G
Olschwang
Sylviane
S
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D005838:Genotype; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D004273:DNA, Neoplasm