TU12B1-TY, a novel gene in the region at 12q22-q23.1 frequently deleted in pancreatic cancer, shows reduced expression in pancreatic cancer cells.

ABSTRACT

Loss of heterozygosity (LOH) on 12q is frequently observed in primary pancreatic cancer, as well as in cancers of other tissues such as stomach and germ cells. LOH correlates with poor prognosis in patients suffering from pancreatic cancer. In quest of tumor suppressor genes in this region, we used bacterial artificial chromosome (BAC) clones to construct a contig to cover one of the two targeted regions previously detected in pancreatic cancer; this region, 12B, is no larger than 650-kb between D12S360 and D12S78 at 12q22-q23.1. While constructing a detailed physical map and placing expressed sequence-tags, we identified a novel human gene, TU12B1-TY. This gene consisted of at least 14 exons and harbored an open reading frame possibly encoding a 473 amino-acid protein. A motif prediction program revealed a transmembrane domain in its carboxyl terminus. Expression in human tissues was found in the brain, placenta, skeletal muscle, pancreas, testis, uterus, and small intestine. In 21 pancreatic cancer cell lines analyzed, we found no structural alteration but all of them showed reduced expression. The present results indicate that reduced function of TU12B1-TY may contribute to the development and/or progression of human pancreatic cancer.