title: Loss of heterozygosity and mutational analyses of the ACTRII gene locus in human colorectal tumors.
abstract: The activin type II receptorgene (ACTRII) is mutated in 58.1% of microsatellite-unstable (MSI-H) colorectal cancers and is a close relative of the TGFbeta-1 type II receptor, which is known to be involved in both MSI-H and non-MSI-H colorectal carcinogenesis. We therefore sought to determine whether ACTRII was involved in non-MSI-H colorectal cancers. We evaluated ACTRII inactivation by allelic deletion, loss of mRNA expression, or somatic mutation in 51 non-MSI-H colon cancers. Loss of heterozygosity (LOH) at the ACTRII locus (2q23.1) was found in 9 (17.6%) of 51 primary tumors. Loss of ACTRII mRNA expression was seen in one (14.3%) of the seven LOH-positive primary tumors from which total RNA was available. We also performed DNA sequencing analysis of tumors showing LOH. One LOH-positive primary tumor exhibited a novel germline missense sequence alteration (amino acid substitution, 117 Ile to Phe) that was not found in 23 additional normal individuals, implying that this alteration is not a frequent polymorphism. We conclude that ACTRII is probably involved in both non-MSI-H and MSI-H colorectal carcinogenesis, but more frequently in the latter subgroup.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine and Baltimore Veteran's Affairs Hospital, Baltimore, Maryland 21201, USA.
authors.forename: Andreea
authors.initials: A
authors.lastname: Olaru
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Mori
authors.forename: Jing
authors.initials: J
authors.lastname: Yin
authors.forename: Suna
authors.initials: S
authors.lastname: Wang
authors.forename: Martha C
authors.initials: MC
authors.lastname: Kimos
authors.forename: Kellie
authors.initials: K
authors.lastname: Perry
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Sato
authors.forename: Florin M
authors.initials: FM
authors.lastname: Selaru
authors.forename: Elena
authors.initials: E
authors.lastname: Deacu
authors.forename: Anca
authors.initials: A
authors.lastname: Sterian
authors.forename: David
authors.initials: D
authors.lastname: Shibata
authors.forename: John M
authors.initials: JM
authors.lastname: Abraham
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Meltzer
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics* / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics; D020125:Mutation, Missense; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D030301:Activin Receptors, Type II