Mertens F, Johansson B, Höglund M, Mitelman F
Department of Clinical Genetics, University Hospital, Lund, Sweden.
Cancer Res. 1997 Jul 1;57(13):2765-80.
To assess the distribution of gains and losses of genetic material in malignant solid neoplasms, 11 tumor types for which at least 100 short-term cultured cases with clonal chromosome aberrations had been reported in the literature were selected. The study was based on cytogenetic information from 508 breast carcinomas, 447 malignant neuroglial tumors, 435 kidney carcinomas, 333 colon carcinomas, 304 ovarian carcinomas, 303 lung carcinomas, 209 testicular germ cell tumors, 206 head and neck carcinomas, 172 malignant melanomas, 142 Wilms' tumors, and 126 neuroblastomas. In each case, the net imbalances were calculated for each chromosome band. The profiles of gains and losses revealed that all tumor types display unique combinations of imbalances. However, there is also considerable overlap among the profiles of the different diagnostic entities, indicating that similar molecular mechanisms may be operative in the development of many types of neoplasia. Deletions were more common than gains in all tumor types, with chromosomes X, Y, 4, 10, 13-15, 18, and 22 and chromosome segments 1p22-pter, 3p13-pter, 6q14-qter, 8p, 9p, and 11p being particularly often deleted in the majority of tumors. To better delineate critical lost segments, deletion profiles based only on structural rearrangements were made for chromosomes 1, 3-12, and 17, which all had on average at least four registered deletions per band. The relative distribution of losses indicated that different bands/regions are affected in different tumor types and that, often, several distinct candidate tumor suppressor gene loci can be discerned within the same chromosome arm, e.g., 1p12-13, 1p22, 1p34, and 1p36 on the short arm of chromosome 1 and 7q22, 7q32, and 7q36 on the long arm of chromosome 7. The only chromosomes or chromosome segments more often gained than deleted were chromosomes 7 and 20 and the long arms of chromosomes 1 and 12, suggesting the presence there of dominantly acting growth-regulatory genes. The data presented in this study should be valuable as a guide for molecular genetic studies on allelic imbalances and for the interpretation of results from studies using comparative genomic hybridization.
为评估恶性实体瘤中遗传物质的得失分布,我们从文献中选取了11种肿瘤类型,每种肿瘤类型至少有100例报道过的具有克隆染色体畸变的短期培养病例。该研究基于508例乳腺癌、447例恶性神经胶质瘤、435例肾癌、333例结肠癌、304例卵巢癌、303例肺癌、209例睾丸生殖细胞肿瘤、206例头颈癌、172例恶性黑色素瘤、142例肾母细胞瘤和126例神经母细胞瘤的细胞遗传学信息。在每个病例中,计算每个染色体带的净失衡情况。得失图谱显示,所有肿瘤类型都呈现出独特的失衡组合。然而,不同诊断实体的图谱之间也存在相当大的重叠,这表明相似的分子机制可能在多种肿瘤的发生发展中起作用。在所有肿瘤类型中,缺失比获得更为常见,在大多数肿瘤中,X、Y、4、10、13 - 15、18和22号染色体以及染色体片段1p22 - pter、3p13 - pter、6q14 - qter、8p、9p和11p特别容易发生缺失。为了更好地描绘关键的缺失片段,我们针对1、3 - 12和17号染色体制作了仅基于结构重排的缺失图谱,这些染色体每个带平均至少有4次记录的缺失。缺失的相对分布表明,不同的带/区域在不同肿瘤类型中受到影响,并且通常在同一染色体臂内可以识别出几个不同的候选肿瘤抑制基因位点,例如1号染色体短臂上的1p12 - 13、1p22、1p34和1p36以及7号染色体长臂上的7q22、7q32和7q36。唯一获得比缺失更频繁的染色体或染色体片段是7号和20号染色体以及1号和12号染色体的长臂,这表明这些区域存在起主导作用的生长调节基因。本研究中呈现的数据对于等位基因失衡的分子遗传学研究以及使用比较基因组杂交的研究结果解释应具有指导价值。