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Molecular, cytogenetic, and phenotypic studies of a constitutional reciprocal translocation t(5; I0)(q22; q25) responsible for familial adenomatous polyposis in a Dutch pedigree
Author(s) -
Van Der Luijt Rob B.,
Tops Carli M. J.,
Khan P. Meera,
Van Der Klift Heleen M.,
Breukel Cor,
Van LeeuwenCornelisse Inge S. J.,
Dauwerse Hans G.,
Beverstock Geoffrey C.,
Van Noort Ellen,
Snel Pleun,
Slors Frederik J. M.,
Vasen Hans F. A.,
Fodde Riccardo
Publication year - 1995
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.2870130309
Subject(s) - familial adenomatous polyposis , adenomatous polyposis coli , chromosomal translocation , biology , genetics , colorectal cancer , germline , gene , microbiology and biotechnology , cancer research , cancer
Familial adenomatous polyposis (FAP) is an inherited predisposition to colorectal cancer caused by germline mutations in the adenomatous polyposis coli ( APC ) gene located on chromosome segment 5q21‐q22. We detected a germline rearrangement of the APC gene in a Dutch FAP family by screening genomic DNA samples with APC cDNA probes. Subsequent molecular and cytogenetic studies revealed a constitutional reciprocal translocation t(5; 10) (q22; q25) that resulted in the disruption of the APC gene. Southern blot and polymorphic marker analysis indicated that part of the APC gene had been deleted. Analysis of the APC protein product indicated that the translocation breakpoint did not lead t o the formation of a detectable truncated APC protein but apparently resulted in a null allele. Evaluation of the clinical phenotypes in the patients suggested that they exhibited features of an unusual form of FAP characterized by a slightly delayed age of onset of colorectal cancer and a reduced number of colorectal polyps. The latter were mainly sessile and were located predominantly in the proximal colon. To our knowledge, this is the first description of FAP caused by a reciprocal translocation disrupting the APC gene. © 1995 Wiley‐Liss, Inc.