TY - JOUR
T1 - Concerted nonsyntenic allelic loss in human colorectal carcinoma
AU - Law, David J.
AU - Olschwang, Sylviane
AU - Monpezat, Jean Philippe
AU - Lefrançois, Danielle
AU - Jagelman, David
AU - Petrelli, Nicholas J.
AU - Thomas, Gilles
AU - Feinberg, Andrew P.
PY - 1988
Y1 - 1988
N2 - Familial polyposis coli (FPC) is caused by an autosomal dominant gene on chromosome 5, and it has been proposed that colorectal cancer in the general population arises from loss or inactivation of the FPC gene, analogous to recessive tumor genes in retinoblastoma and Wilms' tumor. Since allelic loss can be erroneously scored in nonhomogeneous samples, tumor cell populations were first microdissected from 24 colorectal carcinomas, an additional nine cancers were engrafted in nude mice, and nuclei were flow-sorted from an additional two. Of 31 cancers informative for chromosome 5 markers, only 6 (19%) showed loss of heterozygoshy of chromosome 5 alleles, compared to 19 of 34 (56%) on chromosome 17, and 17 of 33 (52%) on chromosome 18. Therefore, it appears that (i) FPC is a true dominant for adenomatosis but not a common recessive gene for colon cancer; and (ii) simple Mendelian models involving loss of alleles at a single locus may be inappropriate for understanding common human solid tumors.
AB - Familial polyposis coli (FPC) is caused by an autosomal dominant gene on chromosome 5, and it has been proposed that colorectal cancer in the general population arises from loss or inactivation of the FPC gene, analogous to recessive tumor genes in retinoblastoma and Wilms' tumor. Since allelic loss can be erroneously scored in nonhomogeneous samples, tumor cell populations were first microdissected from 24 colorectal carcinomas, an additional nine cancers were engrafted in nude mice, and nuclei were flow-sorted from an additional two. Of 31 cancers informative for chromosome 5 markers, only 6 (19%) showed loss of heterozygoshy of chromosome 5 alleles, compared to 19 of 34 (56%) on chromosome 17, and 17 of 33 (52%) on chromosome 18. Therefore, it appears that (i) FPC is a true dominant for adenomatosis but not a common recessive gene for colon cancer; and (ii) simple Mendelian models involving loss of alleles at a single locus may be inappropriate for understanding common human solid tumors.
UR - http://www.scopus.com/inward/record.url?scp=0023705456&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023705456&partnerID=8YFLogxK
U2 - 10.1126/science.2841761
DO - 10.1126/science.2841761
M3 - Article
C2 - 2841761
AN - SCOPUS:0023705456
SN - 0036-8075
VL - 241
SP - 961
EP - 965
JO - Science
JF - Science
IS - 4868
ER -