CDKN2 (MTS1 P16(INK4A)) GENE ALTERATIONS IN ADULT T-CELL LEUKEMIA/LYMPHOMA/

p16(INK4A) is a cyclin-dependent kinase inhibitor (CDKI), and regulate s the cell cycle negatively. Recently, p16(INK4A) protein was shown to be encoded by the CDKN2 gene, which is identical to multiple tumor su ppressor gene 1 (MTS1) on chromosome 9p21, where genetic alterations o ccur frequently in many malignant tumors. As the loss of p16(INK4A) fu nction by genetic alterations leads to inappropriate progression of th e cell cycle, the CDKN2 gene has been investigated intensively as a ne w candidate tumor suppressor gene in many malignant tumors. Adult T-ce ll leukemia/lymphoma (ATLL) is a peripheral T-cell malignancy associat ed with human T-cell lymphotrophic virus type 1 (HTLV-1). As the devel opment to ATL is believed to require not only HTLV 1 infection but als o accumulation of genetic alterations, we investigated the relationshi p between alterations in the CDKN2 gene and ATL. Alterations in the CD KN2 gene were detected in approximately 15 to 20% of ATL patients. Int erestingly, most of the patients with CDKN2 gene alterations had the a ggressive form of ATL. The CDKN2 gene appears to be the major tumor su ppressor gene on chromosome 9p21, and alteration in this gene may play an important role during late stages in the transformation process in duced by HTLV-1.