Bell D W, Jhanwar S C, Testa J R
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Cancer Res. 1997 Sep 15;57(18):4057-62.
Our previous cytogenetic studies of malignant mesotheliomas (MMs) revealed losses from 6q15-21 in approximately 40% of cases, suggestive of recurrent loss of function of a putative tumor suppressor gene(s) located in this chromosome region. To more precisely define the critical region of molecular genetic loss within 6q, we have constructed a high-resolution deletion map of this chromosome arm in 46 MMs. We analyzed 32 microsatellite markers to detect loss of heterozygosity in tumor DNAs. Allelic losses from 6q were observed in a high percentage (61%) of cases. Partial deletions of 6q were identified in 11 cases, and these were used to define four nonoverlapping regions of chromosomal loss: a region involving 6q14-21 (approximately 9 cM; 7 of 11 cases with partial deletions), a region within 6q16.3-21 (approximately 8 cM; 9 cases), a region within 6q21-23.2 (approximately 10 cM; 8 cases), and a distal region located at 6q25 (approximately 13 cM; 9 cases). Most cases exhibited losses from more than one of these regions. We conclude from these data that genomic losses involving 6q in MM are more frequent than previously recognized cytogenetically and that the deletions fall into four discrete locations, suggesting the existence of multiple tumor suppressor loci in 6q that may contribute to the pathogenesis of this malignancy.
我们先前对恶性间皮瘤（MM）的细胞遗传学研究显示，约40%的病例存在6q15 - 21区域的缺失，这提示位于该染色体区域的一个或多个假定肿瘤抑制基因功能反复丧失。为了更精确地界定6q内分子遗传缺失的关键区域，我们构建了46例MM中该染色体臂的高分辨率缺失图谱。我们分析了32个微卫星标记以检测肿瘤DNA中的杂合性缺失。在高比例（61%）的病例中观察到6q的等位基因缺失。在11例病例中鉴定出6q的部分缺失，这些缺失被用于定义四个不重叠的染色体缺失区域：一个涉及6q14 - 21的区域（约9厘摩；11例部分缺失病例中的7例），一个位于6q16.3 - 21内的区域（约8厘摩；9例），一个位于6q21 - 23.2内的区域（约10厘摩；8例），以及一个位于6q25的远端区域（约13厘摩；9例）。大多数病例在这些区域中的不止一个区域出现缺失。从这些数据我们得出结论，MM中涉及6q的基因组缺失比先前细胞遗传学所认识的更为频繁，并且这些缺失落入四个离散位置，提示6q中存在多个肿瘤抑制基因座，它们可能参与了这种恶性肿瘤的发病机制。
