Frequent allelic losses of 9p21 markers and low incidence of mutations at p16(CDKN2) gene in non-Hodgkin lymphomas of B-cell lineage

Abstract

We present an allelotype analysis of 35 cases of non-Hodgkin lymphomas and normal pairs using four microsatellite markers that flank the region occupied by the CDKN2 gene locus at 9p21. Frequent allelic losses (LOH) were detected in B-cell lineage NHLs, including Burkitt lymphoma (33.3% of total, if we only consider high grade tumors). In five of these tumors LOH did not include the CDKN2 gene. Mutational analysis of exon 1 and 2 of CDKN2 (SSGP and sequencing of abnormal bands) revealed a nonsense mutation (Arg72Ter) in one tumor (case 10), where the second hit of the Knudson's model consisted of the elimination of the wild type allele. In view of these results, the hypothesis of two different candidate tumor suppressor gene regions around the CDKN2 locus remains an intriguing possibility.