Genetic instability of adult T-cell leukemia/lymphoma by comparative genomic hybridization analysis.

Abstract

Adult T-cell leukemia/lymphoma (ATL) is a distinct clinicopathological entity, i.e., peripheral T-lymphocytic malignancy caused by human T-lymphotropic virus type I (HTLV-1) with diverse clinical features. High frequency of genetic instability (GIN) in both aggressive and indolent ATL was detected by comparative genomic hybridization (CGH). Among GIN, chromosomal instability, i.e., ancuploidy, in indolent ATL was as frequent but less complex and dynamic as compared to those in aggressive ATL. Some of the CGH alterations, including gain of 14q32, appear to be rather ATL specific. Clonal instability of HTLV-1-infected T cells. i.e., emergence of distinct clone, was detected in about one forth of acute crisis from indolent ATL by CGH and Southern blotting for HTLV-1. Taking together with the previous reports of frequent subtle mutations in several tumor suppressor genes in aggressive ATL, GIN in multistep leukemogenesis of ATL is diverse including clonal, chromosomal, and nucleotide levels.