Cachia A R, Indsto J O, McLaren K M, Mann G J, Arends M J
Department of Tissue and Cell Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, New South Wales, Australia.
Clin Cancer Res. 2000 Sep;6(9):3511-5.
Human melanoma cell lines and tumor tissue from familial and sporadic melanomas have frequent, nonrandom chromosomal breaks and deletions on chromosome 9p21, a region that includes the tumor suppressor gene CDKN2A/p16INK4A. Germ-line mutations within this gene have been observed in some familial melanoma kindreds, but somatic mutation in sporadic primary melanoma is infrequent. Thirty-nine archival, paraffin-embedded, sporadic, primary cutaneous malignant melanomas (20 >3-mm-thick and 19 <0.75-mm-thick cases) were examined for mutations of the CDKN2A gene using single-strand conformational polymorphism analysis and direct sequencing. No mutations were detected. Loss of heterozygosity for the 9p21 microsatellite marker D9S942 was detected in 6 of 17 informative thick lesions (35%) but 0 of 18 thin lesions (P = 0.006). These results support other studies indicating that intragenic mutation is an infrequent mechanism of CDKN2A inactivation in primary melanoma. The finding of loss of heterozygosity for the 9p21 microsatellite D9S942 in thick but not thin primary melanoma suggests that deletion or inactivation of CDKN2A or other tumor suppressor gene(s) at this locus is involved in the progression rather than initiation of sporadic malignant melanoma.
来自家族性和散发性黑色素瘤的人黑色素瘤细胞系及肿瘤组织，在9号染色体短臂21区（9p21）存在频繁的、非随机的染色体断裂和缺失，该区域包含肿瘤抑制基因CDKN2A/p16INK4A。在一些家族性黑色素瘤家系中已观察到该基因的种系突变，但散发性原发性黑色素瘤中的体细胞突变并不常见。利用单链构象多态性分析和直接测序，对39例存档的、石蜡包埋的散发性原发性皮肤恶性黑色素瘤（20例厚度>3mm，19例厚度<0.75mm）进行了CDKN2A基因突变检测。未检测到突变。在17例有信息的厚病变中有6例（35%）检测到9p21微卫星标记D9S942的杂合性缺失，但18例薄病变中未检测到（P = 0.006）。这些结果支持了其他研究，表明基因内突变是原发性黑色素瘤中CDKN2A失活的罕见机制。厚的而非薄的原发性黑色素瘤中9p21微卫星D9S942杂合性缺失的发现表明，该位点的CDKN2A或其他肿瘤抑制基因的缺失或失活参与了散发性恶性黑色素瘤的进展而非起始。
