A refined localization of two deleted regions in chromosome 6q associated with salivary gland carcinomas

Abstract

Deletions within chromosome 6 (6q25 to 6qter) are the most consistent structural change observed in salivary gland carcinomas. To better de®ne the location of these deletions we investigated loss of heterozygosity (LOH) for 23 polymorphic markers within 19 salivary gland carcinomas covering several histological subtypes. LOH was observed in 47% of tumors, con®rming previous reports that such losses are frequent and occur in almost all histological subtypes of tumors. The highest frequency of LOH was found at, or distal to, D6S437. Seven tumors had allelic losses for D6S297 and/or D6S37. A second peak of loss was also observed at D6S262 and D6S32. In some tumors we observed LOH in one or the other of these two regions. In other tumors we observed loss of both regions with retention of intervening loci. These data suggest that two small deletions commonly occur, one between D6S262 and D6S32 (estimated to cover less than 1.5 Mb) and another between D6S297 and D6S446 (estimated to cover *2 Mb). These results extend previous studies by sublocalizing the regions of LOH and suggest that inactivation of one or more tumor suppressor genes located in these regions may be an important step in salivary gland carcinogenesis.

Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type

“…Both aberrations have been found previously by cytogenetic and LOH analyses in salivary gland tumors [11,14,18,22,30] and in ACC [7,23,24,29]. Rao and collaborators [23] reported that gain of chromosome 8 was significantly associated with ACC solid type.…”

DNA Copy Number Gains at Loci of Growth Factors and Their Receptors in Salivary Gland Adenoid Cystic Carcinoma

“…The most frequently detected LOH in salivary gland neoplasms is at locus 6q23-q25 (2,4,6). Although LOH is not detectable by array CGH, we observed one tumor in our group exhibiting a loss in the same chromosomal region.…”

“…Previously reported and frequently changed loci in ACC include gains on 16p, 17q, and 22q13 (20) and losses on 6q (6,20,36) and 12q12-q13 (22). Translocations seem to be conserved to chromosomes 6, 9, and 12 (37,38).…”

Mapping of candidate tumor suppressor genes on chromosome 12 in adenoid cystic carcinoma

“…Cytogenetic, comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) analyses have shown that one of the most frequent genetic changes (deletions and rearrangements) occur on chromosome 6, with other chromosomal changes (such as on 9 and 17) reported less commonly. [1][2][3][4][5][6][7][8][9][10][11][12] In a previous CGH analysis of 24 tumors, we found a previously unreported loss at the 12q12-q13 region. 12 We confirmed our CGH findings by conducting a limited LOH analysis in 29 ACC samples using three chromosome 12 microsatellite markers (D12S391, D12S1301 and D12S1064) to show overall loss on chromosome 12 was similar to that found by CGH analysis.…”