title: PolyA deletions in hereditary nonpolyposis colorectal cancer: mutations before a gatekeeper.
abstract: Microsatellite instability (MSI) secondary to loss of DNA mismatch repair (MMR) is present in adenomas and colorectal carcinomas from individuals with hereditary nonpolyposis colorectal cancer (HNPCC). To better characterize when MMR loss occurs during HNPCC progression, the extent of deletions in noncoding polyA sequences were compared between 6 adenomas (all < or = 1.0 cm in size) and 10 cancers. Numbers of deleted bases reflect time since loss of MMR because polyA deletions are stepwise. Adenoma deletions were nearly the same (85%) as the cancers with sum total deletions at four different polyA loci of -32.7 bases in adenomas and -38.4 bases in cancers. Intervals between negative clinical examinations and tumor removal (average of 2.1 years) were known for six tumors. There were no significant differences in the extent of deletions in tumors removed under clinical surveillance (-34.8 bases) versus tumors removed without prior negative examinations (-36.5 bases). These findings illustrate that MSI is extensive in both small adenomas, and tumors which appear after negative clinical examinations, consistent with an early loss of MMR in HNPCC, even before a gatekeeper mutation.
authors.affiliation: Department of Pathology, Norris Cancer Center, University of Southern California School of Medicine, Los Angeles,California 90033, USA.
authors.forename: Kyoung-Mee
authors.initials: KM
authors.lastname: Kim
authors.forename: Reijo
authors.initials: R
authors.lastname: Salovaara
authors.forename: Jukka-Pekka
authors.initials: JP
authors.lastname: Mecklin
authors.forename: Heikki J
authors.initials: HJ
authors.lastname: Järvinen
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: Darryl
authors.initials: D
authors.lastname: Shibata
mesh_terms: D000236:Adenoma / Q000235:genetics*; D000328:Adult; D020137:Base Pair Mismatch; D002277:Carcinoma / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011061:Poly A / Q000235:genetics*; D011159:Population Surveillance; D013997:Time Factors
chemical_list: D011061:Poly A