A 2·6 Mb interval on chromosome 6q25.2–q25.3 is commonly deleted in human nasal natural killer/T‐cell lymphoma

Abstract

Summary. Natural killer (NK)/T-cell lymphoma is a special subtype of rare malignant lymphoma that is more prevalent in Asia than in America and Europe. This newly characterized haemato-lymphoid malignancy is highly aggressive and frequently present in nasal and upper aerodigestive sites. Several studies have reported the commonly deleted region of chromosome 6q21-25 in this particular type of lymphoma. To refine the smallest region of overlapping (SRO) deletion for localization of potential tumour suppressor (TS) genes, we performed loss of heterozygosity (LOH) and homozygosity mapping of deletion (HOMOD) analyses on 37 nasal and nasal-type NK/T-cell lymphoma patients using a panel of 25 microsatellite markers, covering the 6q21-q25 region. In all patients studied, LOH was detected in eight (89%) paired-sample patients, while hemizygous deletion was detected in three (11%) singlesample patients. Combination of the LOH and HOMOD results defined a distinct 3 Mb SRO on chromosome 6q25. Quantitative multiplex polymerase chain reaction analysis of 10 sequence-tagged sites further refined the putative TS-gene-containing region to a 2AE6 Mb interval between TIAM2 and SNX9. Eighteen known genes/Unigene clusters and 25 hypothetical genes are located within this 2AE6 Mb region, but none are previously identified TS genes. These results provide a framework for future positional cloning of novel TS gene(s) at 6q25.2-q25.3.

Genomic analyses reveal global functional alterations that promote tumor growth and novel tumor suppressor genes in natural killer-cell malignancies

“…7,10,11,21,39 Previous results and our data suggest that 6q21 (B105.6-107 Mb) is the most common aberrant region (Table 1a). Of the eight known genes in the common minimal region of the 6q21 locus, ATG5 and PRDM1 (Blimp-1) had the most consistently low expression.…”

Natural killer-cell malignancies: diagnosis and treatment

“…64 Furthermore, 6q-had also been localized to CD3ÀCD56 þ lymphoma cells, 65 confirming that the chromosomal aberration was restricted to neoplastic NK cells. A commonly deleted region in chromosome 6q21 to 6q25 had been defined by fluorescence ISH and molecular genetic methods, 66,67 Comparative genomic hybridization and loss of heterozygosity studies had shown that, in addition to 6q-, deletions in chromosomes 11q, 13q and 17p were also present. 68,69 The putative genes implicated in these deletions have not been identified.…”

Aspects moléculaires des lymphomes T périphériques (2)

“…Cependant, un mécanisme de trogocytose 1 a été proposé pour expliquer la présence du récepteur au virus sur ces cellules : lors d'un contact rapproché avec une cellule B activée, les cellules NK peuvent acquérir, par transfert de membrane plasmique, le récepteur CD21 et ainsi être infectées par le virus EBV. La prolifération des cellules NK infectées par l'EBV est ensuite favorisée par la production de nombreuses cytokines (interleukine [ 50 % des cas de lymphomes NK/T [6,9,10,17,[19][20][21][22]. Elle s'associe en particulier à la diminution de l'expression du gène PRDM1 (PR domain containing 1) [9].…”