Mitelman Felix, Mertens Fredrik, Johansson Bertil
Department of Clinical Genetics, University Hospital, Lund, Sweden.
Genes Chromosomes Cancer. 2005 Aug;43(4):350-66. doi: 10.1002/gcc.20212.
Chromosome abnormalities have been reported in more than 46,000 benign and malignant neoplastic disorders, leading to the identification of numerous recurrent abnormalities. A substantial number of recurrent balanced aberrations (RBAs), in particular, reciprocal translocations, occur with remarkable specificity in association with clinical and tumor characteristics. This information has become increasingly important both in basic cancer research, as a means to identify pathogenetically important genes, and clinically, as a diagnostic and prognostic instrument. Knowledge of the frequencies of such aberrations thus is of theoretical as well as practical value. However, it is unknown to what extent the data available in the literature reflect reality. A large proportion of the published cases, at least 40%, are biased, in the sense that they were reported because of a specific or unusual karyotypic feature. We have systematically ascertained all RBAs and present data on the frequencies of these abnormalities and their molecular genetic consequences among unselected patients, that is, those studied as part of investigations of consecutive series of individuals with a particular neoplastic disorder. The salient features of the present study are: (1) published data clearly overestimate the prevalence of individual RBAs in most tumor types as well as the proportion of patients having such aberrations. In fact, several well-known published RBAs are not recurrent or have not even been seen among unselected patients, and in no tumor entity, except for chronic myeloid leukemia, does the frequency of unselected cytogenetically abnormal neoplasms with RBAs exceed 35%; (2) the proportions of unselected cases characterized by RBAs among those tumor entities in which at least one RBA has been identified vary considerably both within and among hematologic malignancies, malignant lymphomas, and solid tumors; and (3) the molecular consequences of a substantial proportion, ranging from 19% in hematologic malignancies to 65% in epithelial tumors, of the most common RBAs in unselected patients remain to be clarified.
超过46000例良性和恶性肿瘤性疾病中均有染色体异常的报道，由此发现了众多反复出现的异常情况。特别是大量反复出现的平衡畸变（RBAs），尤其是相互易位，与临床和肿瘤特征相关，具有显著的特异性。这些信息在基础癌症研究中作为识别具有致病重要性的基因的手段，以及在临床上作为诊断和预后工具，都变得越来越重要。因此，了解此类畸变的频率具有理论和实际价值。然而，尚不清楚文献中现有的数据在多大程度上反映了实际情况。至少40%的已发表病例存在偏差，因为它们是由于特定或不寻常的核型特征而被报道的。我们系统地确定了所有的RBAs，并给出了这些异常的频率及其在未经过选择的患者中的分子遗传学后果的数据，即那些作为对患有特定肿瘤性疾病的连续个体系列进行调查的一部分而进行研究的患者。本研究的显著特点是：（1）已发表的数据明显高估了大多数肿瘤类型中单个RBAs的患病率以及具有此类畸变的患者比例。事实上，一些著名的已发表的RBAs并非反复出现，甚至在未经过选择的患者中都未见过，除了慢性粒细胞白血病外，没有任何肿瘤实体中具有RBAs的未经过选择的细胞遗传学异常肿瘤的频率超过35%；（2）在已确定至少一种RBAs的肿瘤实体中，未经过选择的以RBAs为特征的病例比例在血液系统恶性肿瘤、恶性淋巴瘤和实体瘤内部及之间差异很大；（3）未经过选择的患者中，相当一部分最常见的RBAs的分子遗传学后果仍有待阐明，这一比例在血液系统恶性肿瘤中为19%，在上皮性肿瘤中为65%。
