Healy E, Belgaid C E, Takata M, Vahlquist A, Rehman I, Rigby H, Rees J L
Department of Dermatology, University of Newcastle upon Tyne, United Kingdom.
Cancer Res. 1996 Feb 1;56(3):589-93.
A multistep genetic model of tumorigenesis, based on genetic alterations in benign and primary malignant lesions, has been proposed for neoplasms such as colonic carcinoma. However, evidence for a similar genetic progression in melanoma has relied heavily on findings in cultured lesions or metastases. We have investigated every autosomal arm for loss of heterozygosity in 41 primary cutaneous melanomas and 32 benign melanocytic nevi, and have investigated several chromosome arms that show loss in melanoma in 27 Spitz nevi (a nevus with histological similarities to melanoma). Loss of heterozygosity in primary melanoma was identified most frequently on chromosomes 9p (46%) at loci near the p16INK4 gene, 10q (31%), 6q (31%), and 18q (22%); loss of these chromosome arms were related to the progression of the melanoma. Only two benign melanocytic nevi (both of which showed atypical features on histology) demonstrated genetic alterations, including p9 loss in one case. In addition, two Spitz nevi contained interstitial deletions on chromosome 9p. Our findings show that loss of heterozygosity of 9p is not confined to melanoma, but that other uncultured melanocytic lesions can also display loss of this chromosome arm, and that other genetic changes (e.g., loss of 10q, 6q, and 18q) may be important in conveying the malignant phenotype to melanoma.
基于良性和原发性恶性病变中的基因改变，已经提出了一种用于结肠癌等肿瘤的多步骤肿瘤发生遗传模型。然而，黑色素瘤中类似基因进展的证据在很大程度上依赖于培养病变或转移灶中的发现。我们研究了41例原发性皮肤黑色素瘤和32例良性黑素细胞痣中每个常染色体臂的杂合性缺失情况，并研究了27例Spitz痣（一种在组织学上与黑色素瘤相似的痣）中在黑色素瘤中显示缺失的几个染色体臂。原发性黑色素瘤中杂合性缺失最常出现在9号染色体短臂（46%）靠近p16INK4基因的位点、10号染色体长臂（31%）、6号染色体长臂（31%）和18号染色体长臂（22%）；这些染色体臂的缺失与黑色素瘤的进展有关。只有两个良性黑素细胞痣（两者在组织学上均显示非典型特征）表现出基因改变，其中一例为9号染色体短臂缺失。此外，两个Spitz痣在9号染色体短臂上存在间质缺失。我们的研究结果表明，9号染色体短臂的杂合性缺失并不局限于黑色素瘤，其他未经培养的黑素细胞病变也可能出现该染色体臂的缺失，并且其他基因改变（如10号染色体长臂、6号染色体长臂和18号染色体长臂的缺失）可能在将恶性表型传递给黑色素瘤方面具有重要意义。
