De Rienzo A, Balsara B R, Apostolou S, Jhanwar S C, Testa J R
Human Genetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Oncogene. 2001 Sep 27;20(43):6245-9. doi: 10.1038/sj.onc.1204828.
Previous comparative genomic hybridization and allelic loss analyses demonstrated frequent deletions from 15q11.1-15 in malignant mesothelioma. Recurrent losses of 15q11-22 have also been reported in several other tumor types such as breast and colorectal cancers. To more precisely map the commonly deleted region, we have performed a high density loss of heterozygosity analysis of 46 malignant mesotheliomas, using 26 polymorphic microsatellite markers spanning the entire long arm of chromosome 15. Allelic loss from 15q was observed in 22 of 46 (48%) cases. These analyses have defined a minimally deleted region of approximately 3-cM, which was confirmed to reside at 15q15 by fluorescence in situ hybridization analysis with yeast artificial chromosome probes. No tumor suppressor genes have been reported to map to this site. The minimally deleted region identified in this investigation overlaps those observed in other kinds of cancer, and is the smallest site of recurrent 15q loss identified to date in human tumors. The identification of this commonly deleted site implicates a putative tumor suppressor gene(s) at 15q15 involved in diverse forms of human neoplasia.
先前的比较基因组杂交和等位基因缺失分析表明,恶性间皮瘤中15q11.1-15区域经常发生缺失。15q11-22区域的反复缺失在其他几种肿瘤类型中也有报道,如乳腺癌和结直肠癌。为了更精确地定位常见缺失区域,我们使用跨越15号染色体整个长臂的26个多态性微卫星标记,对46例恶性间皮瘤进行了高密度杂合性缺失分析。在46例病例中的22例(48%)观察到15q等位基因缺失。这些分析确定了一个约3厘摩的最小缺失区域,通过酵母人工染色体探针的荧光原位杂交分析证实该区域位于15q15。尚未有肿瘤抑制基因定位于此位点的报道。本研究中确定的最小缺失区域与在其他类型癌症中观察到的区域重叠,是迄今为止在人类肿瘤中确定的15q反复缺失的最小位点。该常见缺失位点的确定提示15q15处存在一个假定的肿瘤抑制基因,参与多种人类肿瘤的发生。