Gerhard D S, Dracopoli N C, Bale S J, Houghton A N, Watkins P, Payne C E, Greene M H, Housman D E
Nature. 1987;325(6099):73-5. doi: 10.1038/325073a0.
It was recently reported that different rare alleles at the Ha-ras-1 locus occurred at a significantly higher combined frequency in cancer patients than in an unaffected population. In particular, melanoma patients were reported to have a significantly higher frequency of such alleles. We have examined the frequency of rare Ha-ras-1 alleles in a large number of cases of sporadic melanoma. Our results indicate that the distribution of rare alleles in this population does not differ from that found in normal populations. Also, to test the hypothesis that a hereditary predisposition to melanoma could be inherited via an allele at the Ha-ras-1 locus, we examined the transmission of the segment of the short arm of chromosome 11 (11p) carrying the Ha-ras-1 locus in a number of families previously shown to exhibit a hereditary predisposition to melanoma and its precursor lesion, the dysplastic nevus syndrome (DNS). Our genetic linkage results thus obtained strongly exclude the association of a predisposition to melanoma or the precursor lesion with the inheritance of the Ha-ras-1 locus or the segment of chromosome 11 on which it is located. These results imply that hereditary predisposition to melanoma is associated with genes other than the Ha-ras-1 locus, contradicting the original suggestion of Krontiris et al., made on the basis of either an inadequate sample size or other misleading experimental factors.
最近有报道称，癌症患者中Ha-ras-1基因座处不同的稀有等位基因组合频率显著高于未受影响人群。特别是，据报道黑色素瘤患者中此类等位基因的频率显著更高。我们检测了大量散发性黑色素瘤病例中稀有Ha-ras-1等位基因的频率。我们的结果表明，该人群中稀有等位基因的分布与正常人群中发现的分布没有差异。此外，为了检验黑色素瘤的遗传易感性可能通过Ha-ras-1基因座的一个等位基因遗传的假设，我们检测了11号染色体短臂（11p）上携带Ha-ras-1基因座的片段在一些先前已显示出对黑色素瘤及其前体病变发育异常痣综合征（DNS）具有遗传易感性的家族中的传递情况。我们由此获得的遗传连锁结果强烈排除了黑色素瘤或前体病变的易感性与Ha-ras-1基因座或其所在的11号染色体片段的遗传之间的关联。这些结果意味着黑色素瘤的遗传易感性与Ha-ras-1基因座以外的基因有关，这与Krontiris等人基于样本量不足或其他误导性实验因素所提出的最初观点相矛盾。
