Molecular definition of a chromosome 9p21 germ-line deletion in a woman with multiple melanomas and a plexiform neurofibroma: implications for 9p tumor-suppressor gene(s).

摘要: Cutaneous malignant melanoma (CMM) is often familial, but the mode of inheritance and chromosomal location susceptibility locus are controversial. Identification a 34-year-old woman with eight primary melanomas, multiple atypical moles, de novo constitutional cytogenetic rearrangement involving chromosomes 5p 9p suggested presence predisposition gene at one these locations. A high-resolution karyotype showed partial deletion dark-staining Giemsa band, either 5p14 or 9p21. The patient was heterozygous for five RFLPs. In situ hybridization D9S3 indicated that this 9p21 marker deleted. Gene dosage studies demonstrated two more distal markers, D9S126 IFNA. addition, she hemizygous proximal short tandem-repeat polymorphism D9S104. D9S18, D9S19, D9S33 were retained, localizing to between D9S19 on side side. Pulsed-field gel electrophoresis did not reveal any junction fragments in patient's DNA. This germ-line suggests mutations may initiate tumorigenesis.