Petty E M, Gibson L H, Fountain J W, Bolognia J L, Yang-Feng T L, Housman D E, Bale A E
Departments of Genetics, Yale University School of Medicine, New Haven, Cambridge.
Am J Hum Genet. 1993 Jul;53(1):96-104.
Cutaneous malignant melanoma (CMM) is often familial, but the mode of inheritance and the chromosomal location of melanoma susceptibility locus are controversial. Identification of a 34-year-old woman with eight primary malignant melanomas, multiple atypical moles, and a de novo constitutional cytogenetic rearrangement involving chromosomes 5p and 9p suggested the presence of a melanoma predisposition gene at one of these locations. A high-resolution karyotype showed a partial deletion of a dark-staining Giemsa band, either 5p14 or 9p21. The patient was heterozygous for five 5p14 RFLPs. In situ hybridization with D9S3 indicated that this 9p21 marker was deleted. Gene dosage studies demonstrated the deletion of two more distal 9p21 markers, D9S126 and IFNA. In addition, she was hemizygous for the more proximal 9p21 short tandem-repeat polymorphism at D9S104. D9S18, D9S19, and D9S33 were retained, localizing the deletion to 9p21 between D9S19 on the proximal side and D9S33 on the distal side. Pulsed-field gel electrophoresis with D9S19 and D9S33 did not reveal any junction fragments in the patient's DNA. This germ-line deletion suggests that mutations in a 9p21 gene may initiate melanoma tumorigenesis.
皮肤恶性黑色素瘤（CMM）通常具有家族性，但黑色素瘤易感基因座的遗传模式和染色体定位存在争议。一名34岁女性患有8处原发性恶性黑色素瘤、多个非典型痣，并且存在涉及5号染色体短臂（5p）和9号染色体短臂（9p）的新生染色体组型重排，这表明在这些位置之一存在黑色素瘤易感基因。高分辨率核型分析显示一条深染的吉姆萨带部分缺失，要么是5p14，要么是9p21。该患者对于5个5p14限制性片段长度多态性（RFLP）呈杂合状态。用D9S3进行原位杂交表明该9p21标记缺失。基因剂量研究证实另外两个位于9p21远端的标记D9S126和IFNA缺失。此外，她在更靠近近端的D9S104处的9p21短串联重复多态性上呈半合子状态。D9S18、D9S19和D9S33保留，将缺失定位在近端的D9S19和远端的D9S33之间的9p21区域。用D9S19和D9S33进行脉冲场凝胶电泳未在患者DNA中发现任何连接片段。这种种系缺失提示9p21基因中的突变可能引发黑色素瘤的肿瘤发生。
