Balsara B R, Bell D W, Sonoda G, De Rienzo A, du Manoir S, Jhanwar S C, Testa J R
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Cancer Res. 1999 Jan 15;59(2):450-4.
Comparative genomic hybridization analysis was performed to identify chromosomal imbalances in 24 human malignant mesothelioma (MM) cell lines derived from untreated primary tumors. Chromosomal losses accounted for the majority of genomic imbalances. The most frequent underrepresented segments were 22q (58%) and 15q1.1-21 (54%); other recurrent sites of chromosomal loss included 1p12-22 (42%), 13q12-14 (42%), 14q24-qter (42%), 6q25-qter (38%), and 9p21 (38%). The most commonly overrepresented segment was 5p (54%). DNA sequence amplification at 3p12-13 was observed in two cases. Whereas some of the regions of copy number decreases (i.e., segments in 1p, 6q, 9p, and 22q) have previously been shown to be common sites of karyotypic and allelic loss in MM, our comparative genomic hybridization analyses identified a new recurrent site of chromosomal loss within 15q in this malignancy. To more precisely map the region of 15q deletion, loss of heterozygosity analyses were performed with a panel of polymorphic microsatellite markers distributed along 15q, which defined a minimal region of chromosomal loss at 15q11.1-15. The identification of frequent losses of a discrete segment in 15q suggests that this region harbors a putative tumor suppressor gene whose loss/inactivation may contribute to the pathogenesis of many MMs.
进行比较基因组杂交分析,以鉴定源自未经治疗的原发性肿瘤的24个人类恶性间皮瘤(MM)细胞系中的染色体失衡情况。染色体缺失占基因组失衡的大部分。最常见的代表性不足片段是22q(58%)和15q1.1 - 21(54%);其他反复出现染色体缺失的位点包括1p12 - 22(42%)、13q12 - 14(42%)、14q24 - qter(42%)、6q25 - qter(38%)和9p21(38%)。最常见的代表性过度片段是5p(54%)。在两例中观察到3p12 - 13处的DNA序列扩增。虽然一些拷贝数减少的区域(即1p、6q、9p和22q中的片段)先前已被证明是MM中核型和等位基因缺失的常见位点,但我们的比较基因组杂交分析在这种恶性肿瘤中鉴定出15q内一个新的反复出现的染色体缺失位点。为了更精确地定位15q缺失区域,使用一组沿15q分布的多态性微卫星标记进行杂合性缺失分析,确定了15q11.1 - 15处染色体缺失的最小区域。15q中一个离散片段频繁缺失的鉴定表明,该区域含有一个假定的肿瘤抑制基因,其缺失/失活可能促成许多MM的发病机制。