No abstract

A unique microRNA signature is associated with prognostic factors and disease progression in CLL. Mutations in microRNA transcripts are common and may have functional importance.

These results suggest that alteration in microRNA expression is related to endocrine and acinar neoplastic transformation and progression of malignancy, and might prove useful in distinguishing tumors with different clinical behavior.

The Testin (TES) gene was previously identified as a putative human tumor suppressor gene at 7q31.2, a region that is frequently deleted in hematopoietic malignancies, as well as in epithelial tumors. To determine whether TES acts as a tumor suppressor in vivo, we generated a Tes knockout mouse and then used it in an established model of carcinogen-induced gastric cancer. In mice a zinc-deficient (ZD) diet enhances cellular proliferation in the forestomach and susceptibility to N-nitrosomethylbenzylamine (NMBA)-induced carcinogenesis. Five-week-old Tes wild-type (؉͞؉), heterozygous (؉͞؊), and homozygous (؊͞؊) mice were divided into four groups: mice fed a zinc-sufficient diet (ZS); mice fed a ZD diet; ZS fed plus NMBA-treated mice (ZS؉NMBA), and ZD fed plus NMBA-treated mice (ZD؉NMBA). After 4 weeks, the ZS؉NMBA and ZD؉NMBA groups were treated with three intragastric doses of NMBA. Animals were killed 8 weeks after NMBA administration: 25% of ؉͞؉ mice developed benign lesions; 88% of ؉͞؊ showed multiple papillomas, atypical glandular metaplasia, and squamous cell carcinomasl; and 81% of ؊͞؊ mice displayed very large papillomas, squamous cell carcinomas, and adenocarcinomas. A statistically significant difference in tumor incidence was found between ؉͞؊ versus ؉͞؉ and ؊͞؊ versus ؉͞؉ (P < 0.0001). These data suggest that Tes functions as a tumor suppressor gene in vivo.carcinogen-induced tumorigenesis ͉ gastric cancer ͉ TES ͉ gene targeting