Alteration of chromosome arm 6p is characteristic of primary mediastinal B-cell lymphoma, as identified by genome-wide allelotyping

Five cases of primary mediastinal B-cell lymphoma (PMBL) each have been stu died with 375 microsatellite markers from all 22 autosomes. Of the 151 geno mic alterations among the 1,875 assays, only five were allelic losses. The remainder of the microsatellite alterations consisted of 114 allelic imbala nces and 32 instabilities. Microsatellite alterations were found in all cas es on chromosomal arms 6p and 9p. These allelic imbalances most likely are indicative of genetic amplification, a finding agreeing well with those of studies using either comparative genomic hybridization or arbitrarily prime d polymerase chain reaction, in which amplification of chromosome arm 9p in PMBL has been found. The allelic imbalances on chromosome arm 6p always in cluded marker D6S276 located at 6p21.3-p22.3, where the MHC class I genes r eside. These allelic imbalances may be reflective of alterations in the exp ression of the MHC gene products, characteristic of PM BL. Allelic anomalie s close to the MYB gene locus on 6q were detected in two cases and prompted the analysis of MYB rearrangements in a series of 30 lymphomas. One rearra ngement was detected in one of 18 cases of PMBL and in none of 10 diffuse, large B-cell lymphomas and two T-cell lymphomas. Our genome-wide microsatel lite analysis provides independent confirmation that PMBL is characterized by infrequent chromosomal tosses and by frequent genetic alterations involv ing chromosomal arm 9p. For the first time, chromosomal arm 6p has been ide ntified as a highly frequent target of genetic alterations in this tumor ty pe. Finally, MYB may also be involved occasionally in PMBL pathogenesis. (C ) 2001 Wiley-Liss, Inc.