Loss of Heterozygosity and Mutational Analyses of the ACTRII Gene Locus in Human Colorectal Tumors
| Autor: | Martha Kimos, Fumiaki Sato, Jing Yin, Elena Deacu, Yan Xu, David Shibata, Anca Sterian, Andreea Olaru, Stephen J. Meltzer, Yuriko Mori, Florin M. Selaru, John M. Abraham, Kellie Perry, Suna Wang |
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| Rok vydání: | 2003 |
| Předmět: |
Activin Receptors
Type II DNA Mutational Analysis Mutation Missense Loss of Heterozygosity Adenocarcinoma Biology medicine.disease_cause Germline Pathology and Forensic Medicine Loss of heterozygosity Germline mutation medicine Humans Missense mutation RNA Messenger RNA Neoplasm Allele neoplasms Molecular Biology Reverse Transcriptase Polymerase Chain Reaction Point mutation DNA Neoplasm Cell Biology medicine.disease Primary tumor digestive system diseases Gene Expression Regulation Neoplastic Cancer research Colorectal Neoplasms Carcinogenesis Microsatellite Repeats |
| Zdroj: | Laboratory Investigation. 83:1867-1871 |
| ISSN: | 0023-6837 |
| DOI: | 10.1097/01.lab.0000106723.75567.72 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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