Yang-Feng T L, Han H, Chen K C, Li S B, Claus E B, Carcangiu M L, Chambers S K, Chambers J T, Schwartz P E
Department of Genetics, Yale University School of Medicine, New Haven, CT.
Int J Cancer. 1993 Jun 19;54(4):546-51. doi: 10.1002/ijc.2910540405.
Loss of heterozygosity (LOH) was examined at 86 loci distributed on every chromosomal arm in 50 human ovarian tumors. Frequent allele losses were observed on chromosomes 13q (42%), 17p (42%), 17q (45%), and Xp (41%). Deletion mapping on chromosome 17 revealed a candidate gene on the long arm distal to D17S41/S74 for ovarian cancer which is distant from the locus for early onset breast cancer. LOH on chromosome 17q was found to be concordant with LOH on chromosomes 3p, 13q, 17p and Xp suggesting that it may be an early event in neoplastic development. These findings indicate that multiple tumor-suppressor genes for ovarian cancer possibly exist on chromosomes 13q, 17, and/or Xp and provide the basis for the identification of candidate gene(s) associated with ovarian cancer. The chromosomal mechanisms resulting in allele losses in ovarian cancer include deletion, deletion/duplication, mitotic recombination and monosomy, in concordance with the developed genetic model.
在50例人类卵巢肿瘤中,对分布于各染色体臂上的86个位点进行了杂合性缺失(LOH)检测。在13号染色体长臂(42%)、17号染色体短臂(42%)、17号染色体长臂(45%)和X染色体短臂(41%)上观察到频繁的等位基因缺失。17号染色体上的缺失定位揭示了一个位于D17S41/S74远端长臂上的卵巢癌候选基因,该基因与早发性乳腺癌的位点距离较远。发现17号染色体长臂上的LOH与3号染色体短臂、13号染色体长臂、17号染色体短臂和X染色体短臂上的LOH一致,提示其可能是肿瘤发生发展中的早期事件。这些发现表明,卵巢癌的多个肿瘤抑制基因可能存在于13号染色体长臂、17号染色体和/或X染色体短臂上,并为鉴定与卵巢癌相关的候选基因提供了依据。导致卵巢癌等位基因缺失的染色体机制包括缺失、缺失/重复、有丝分裂重组和单体型,这与已建立的遗传模型一致。