Mathew C G, Smith B A, Thorpe K, Wong Z, Royle N J, Jeffreys A J, Ponder B A
Nature. 1987;328(6130):524-6. doi: 10.1038/328524a0.
Recent studies have identified normal cellular DNA sequences which are lost in the development of embryonal and adult tumours. These tumours are thought to arise after a primary mutation in one allele of such a sequence is followed by loss of its normal homologue. In familial cases, the primary mutation is transmitted in the germ line. The secondary mutation may involve a substantial loss of chromosomal material and thus lead to identification of the site of the inherited mutation. We have examined constitutional and tumour genotypes of medullary thyroid carcinomas and phaeochromocytomas which develop in the dominantly inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN2) to locate the predisposing gene in this syndrome. We observed deletion of a hypervariable region of DNA on the short arm of chromosome 1 in seven out of fourteen tumours. Analysis of the parental origin of the deleted allele in two families showed that it was derived from the affected parent in one case, which suggests that the deletion does not reflect the site of the inherited mutation in MEN2. The deleted region is distal to the breakpoint commonly detected in neuroblastomas, which share with the tumours of MEN2 embryological origin from neuroectoderm.
最近的研究已经鉴定出在胚胎肿瘤和成人肿瘤发生过程中丢失的正常细胞DNA序列。这些肿瘤被认为是在这样一个序列的一个等位基因发生原发性突变后，其正常同源物丢失而产生的。在家族性病例中，原发性突变通过种系传递。继发性突变可能涉及染色体物质的大量丢失，从而导致确定遗传性突变的位点。我们已经检查了在显性遗传癌症综合征多发性内分泌腺瘤2型（MEN2）中发生的甲状腺髓样癌和嗜铬细胞瘤的体质基因型和肿瘤基因型，以定位该综合征中的易感基因。我们在14个肿瘤中的7个中观察到1号染色体短臂上一个DNA高变区的缺失。对两个家族中缺失等位基因的亲本来源分析表明，在一个病例中它来自受影响的亲本，这表明该缺失并不反映MEN2中遗传性突变的位点。该缺失区域位于神经母细胞瘤中通常检测到的断点的远端，神经母细胞瘤与MEN2的肿瘤具有神经外胚层的胚胎学起源。
