Bale S J, Greene M H, Murray C, Goldin L R, Johnson A H, Mann D
Int J Cancer. 1985 Oct 15;36(4):439-43. doi: 10.1002/ijc.2910360405.
Detailed HLA typing was performed in 11 families with hereditary cutaneous malignant melanoma (CMM) and dysplastic nevi to determine if the melanoma susceptibility locus was genetically linked to the major histocompatibility complex. Previously published data from 19 other families were re-analyzed in the same manner. When data from all 30 families were pooled and CMM was defined as the disease trait, the hypothesis of linkage was rejected for all values of recombination (theta) less than 40%. Data on family members' status regarding dysplastic nevi (DN), a well-characterized precursor of hereditary CMM, were available for our 11 families and 7 previously-reported families. Linkage analysis between the combined CMM/DN trait and HLA provided strong evidence against this hypothesis. Significant heterogeneity was observed when various sub-groups of families were compared; these data suggested that preferential reporting of positive linkage findings and misclassification of study subjects' CMM susceptibility status may have contributed to previous beliefs that the hereditary melanoma gene was linked to HLA. When our data are combined with previously-published information, we conclude that there is strong evidence against linkage of a CMM/DN gene with the major histocompatibility complex.
对11个患有遗传性皮肤恶性黑色素瘤（CMM）和发育异常痣的家族进行了详细的HLA分型，以确定黑色素瘤易感基因座是否与主要组织相容性复合体存在遗传连锁关系。以同样的方式对之前发表的来自其他19个家族的数据进行了重新分析。当汇总所有30个家族的数据并将CMM定义为疾病性状时，对于所有重组值（θ）小于40%的情况，连锁假设均被拒绝。我们的11个家族以及之前报道的7个家族提供了家庭成员关于发育异常痣（DN）（遗传性CMM的一种特征明确的前驱病变）状态的数据。对CMM/DN联合性状与HLA之间进行连锁分析，有力地反驳了这一假设。在比较不同家族亚组时观察到显著的异质性；这些数据表明，之前关于遗传性黑色素瘤基因与HLA连锁的观点，可能是由于对阳性连锁结果的优先报道以及研究对象CMM易感性状态的错误分类所致。当我们的数据与之前发表的信息相结合时，我们得出结论，有充分证据反对CMM/DN基因与主要组织相容性复合体存在连锁关系。
