Frameshift mutations of human gastrin receptor gene (hGARE) in gastrointestinal cancers with microsatellite instability.

摘要: Gastrointestinal tumors with DNA mismatch repair (MMR) defects show microsatellite instability (MSI) and harbor frameshift mutations in coding mononucleotide repeats of cancer-related genes (targets). We assessed MSI status 233 sporadic gastrointestinal tumors. classified as MSI-H (high-frequency instability) 15 (10%) 150 colorectal cancers 13 (16%) 83 gastric cancers. searched for a poly(T)(8) tract within the gastrin receptor gene (hGARE), which has potential role carcinogenesis. To this purpose, we screened 43 unstable (including hereditary nonpolyposis cancer cases previously MSI-H), 98 stable tumors, well 3 MMR-deficient 4 MMR-proficient cell lines. found 8 (19%) but none hGARE mutation frequency was similar (23%) cancers, including (13%) (20%) cases. All mutated proved to other that are considered targets tumorigenesis. The gastrin-sensitive LoVo cells also showed heterozygous mutation, expressed only allele. detected can be predicted generate truncated protein carrying amino acid changes. On basis genetic findings, propose new candidate target Functional studies warranted elucidate mechanism by might contribute