AMY2A: a possible tumor-suppressor gene of 1p21.1 loss in gastric carcinoma.

Homozygous deletions (HDs) are major genomic forces contributing to the development of many solid tumors. To identify critical tumor-suppressor loci involved in the pathogenesis of gastric carcinoma (GC), a high-resolution microarray-CGH was performed in a series of 27 GC patients. On a genome-wide profile, five distinct HD (log2 ratio <-1) loci, including 1p21.1, 2q21.1, 10q24.32, 13q34 and 15q11.2 were identified. These regions contained representative tumor-related genes, such as the FGF8 and NPM3 genes at 10q24.32, and the LAMP1 gene at 13q34, which have been reported in connection with various tumors. The most frequent HD encompassed chromosome band 1p21.1 in 5 of 27 GC cases (18.5%). A hemizygous deletion (-0.5< log2 ratio < or = -1) or a single copy loss (log2 ratio <-0.25) from the 1p21.1 region was noted in 51.9% (14/27) and 88.9% (24/27) of GCs, respectively. A 30 Kb HD of the 1p21.1 chromosomal region was shown to contain a potential candidate tumor-suppressor gene (TSG) of AMY2A. Quantitative real time PCR analysis further confirmed complete loss of expression of the AMY2A gene located at the 1p21.1 region. We demonstrated that AMY2A, a possible TSG, is frequently silenced in GC deletion 1p21.1. The identified gene could provide a basis for further functional validation and may lead to the identification of novel candidates for tumorigenesis and targeted therapies in GC.