LOSS OF ALLELES FROM THE DISTAL SHORT ARM OF CHROMOSOME-1 OCCURS LATE IN MELANOMA TUMOR PROGRESSION
LOSS OF ALLELES FROM THE DISTAL SHORT ARM OF CHROMOSOME-1 OCCURS LATE IN MELANOMA TUMOR PROGRESSION
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DOI：
10.1073/pnas.86.12.4614
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发表时间：
1989-06-01
影响因子：
11.1
通讯作者：
KEFFORD, RF
中科院分区：
文献类型：
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作者：
DRACOPOLI, NC;HARNETT, P;KEFFORD, RF
家族性恶性黑色素瘤及其前体病变——发育不良痣的基因被分配到1号染色体远端短臂的一个区域，该区域经常与黑色素瘤细胞的核型异常有关。我们在35个黑素瘤和31个黑素瘤细胞系中检查了染色体1p上的基因座，以分析这些异常在黑素细胞转化中的作用。在15/35（43%）的黑色素瘤细胞系和11/21（52%）的黑色素瘤细胞系中发现染色体1p位点的杂合性缺失。对来自同一患者的多个转移瘤以及来自遗传性黑色素瘤家族的黑色素瘤和淋巴母细胞样细胞样本的分析表明，远端1p位点杂合性的缺失是肿瘤进展的晚期事件，而如果黑色素瘤是由于细胞隐性机制造成的，则会发生第二次突变。与神经母细胞瘤和多发性内分泌瘤（MEN2）的比较表明，这些恶性肿瘤中常见的1p杂合性缺失是神经外胚层肿瘤进展的常见晚期事件。
The gene for familial malignant melanoma and its precursor lesion, the dysplastic nevus, has been assigned to a region of the distal short arm of chromosome 1, which is frequently involved in karyotypic abnormalities in melanoma cells. We have examined loci on chromosome 1p for loss-of-constitutional heterozygosity in 35 melanomas and 31 melanoma cell lines to analyse the role of these abnormalities in melanocyte transformation. Loss-of-heterozygosity at loci on chromosome 1p was identified in 15/35 (43%) melanomas and 11/21 (52%) melanoma cell lines. Analysis of multiple metastases derived from the same patient and of melanoma and lymphoblastoid samples from a family with hereditary melanoma showed that the loss-of-heterozygosity at loci on distal 1p is a late event in tumor progression, rather than the second mutation that would occur if melanoma were due to a cellular recessive mechanism. Comparisons with neuroblastoma and multiple endocrine neoplasia (MEN2) suggest that the frequent 1p loss-of-heterozygosity in these malignancies is a common late event of neuroectodermal tumor progression.