Abstract：
:New facets to Knudson's [corrected] "two-hit" hypothesis have been proposed recently in relation to adenomatous polyposis coli (APC): protein inactivation may be selected weakly, and the two hits may be interdependent. We reviewed published data on 165 sporadic and 102 familial adenomatous polyposis-associated colorectal tumors with two characterized mutations. Using a Poisson model, we redefined the mutation cluster region (MCR) to residues 1281-1556 and confirmed that the locations of pairs of APC mutations are interdependent (P < 0.0001). A mathematical model, based on the data for sporadic tumors, implied different growth advantages for different combinations of APC mutations: genotype I/I (I: mutation inside MCR) was 3.9 times more likely to be selected than IO or IL (O: mutation outside MCR, L: allelic loss), which were 27.8 times more likely to be selected than OO or OL.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Cheadle JP,Krawczak M,Thomas MW,Hodges AK,Al-Tassan N,Fleming N,Sampson JRsubject
Has Abstractpub_date
2002-01-15 00:00:00pages
363-6issue
2eissn
0008-5472issn
1538-7445journal_volume
62pub_type
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