Jolly K W, Malkin D, Douglass E C, Brown T F, Sinclair A E, Look A T
Department of Experimental Oncology and Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
Oncogene. 1994 Jan;9(1):97-102.
Germline mutations within evolutionary conserved exons of the p53 gene predispose to tumor development in several familial cancer syndromes. We now report identification of a novel p53 mutation affecting the splice acceptor site of exon 6 in the germline DNA of a family with hereditary breast-ovarian cancer. This splice-site mutation, which results in omission of exon 6 and creates a frame-shift and premature stop codon in transcripts from the mutant allele, was found in seven family members--four of whom have developed breast, ovarian or choroid plexus tumors before age 35. Our finding suggests the need to examine the entire p53 gene for splice-site, frame-shift, and nonsense (as well as missense) mutations in families with early-onset hereditary breast and breast-ovarian cancers not linked to the BRCA1 gene on chromosome 17q. We propose that the term 'p53 familial cancer syndrome' be applied to clusters of tumors in families with documented germline p53 mutations, regardless of the histopathologic findings or pattern of tumor development.
p53基因进化保守外显子内的种系突变在几种家族性癌症综合征中易引发肿瘤。我们现在报告在一个遗传性乳腺癌-卵巢癌家族的种系DNA中鉴定出一种影响外显子6剪接受体位点的新型p53突变。这种剪接位点突变导致外显子6缺失，并在突变等位基因的转录本中产生移码和提前终止密码子，在7名家族成员中被发现，其中4人在35岁之前就患上了乳腺癌、卵巢癌或脉络丛肿瘤。我们的发现表明，对于未与17号染色体上的BRCA1基因连锁的早发性遗传性乳腺癌和乳腺癌-卵巢癌家族，有必要检查整个p53基因的剪接位点、移码和无义（以及错义）突变。我们建议将“p53家族性癌症综合征”这一术语应用于有记录的种系p53突变家族中的肿瘤集群，而不考虑组织病理学发现或肿瘤发展模式。
