Van Gele M, Leonard J H, Van Roy N, Cook A L, De Paepe A, Speleman F
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Int J Cancer. 2001 May 1;92(3):409-13. doi: 10.1002/ijc.1209.
Merkel cell carcinoma (MCC) is a rare, highly metastatic skin tumor of neuroectodermal origin. The disease shares clinical and histopathological features with small cell lung carcinoma (SCLC). The genetic mechanisms underlying the development and tumor progression of MCC are poorly understood. We recently showed by comparative genomic hybridization (CGH) that the pattern of chromosomal abnormalities in MCC resembles that of SCLC. One of the most frequently observed losses involved the entire chromosome 10 or partial loss of the chromosome 10 long arm (33% of examined MCC cases). The PTEN tumor-suppressor gene has been mapped to 10q23.3 and was shown to be mutated in a variety of human cancers including SCLC. Germline PTEN mutations have been observed in familial predisposing cancer syndromes including Cowden disease. Interestingly, an association between Cowden syndrome and Merkel cell carcinoma has been reported. To study the possible role of PTEN in MCC oncogenesis, loss of heterozygosity (LOH) analysis for the 10q23 region was performed on 26 MCC tumor samples from 23 MCC patients. The PTEN locus was deleted in 9 of 21 (43%) informative MCC tumor samples [7 of 18 (39%) MCC patients]. Despite this high frequency of LOH at 10q23, mutation and homozygous deletion screening of the PTEN gene revealed only one tumor with a nonsense mutation and a second with a homozygous deletion of exon 9. These data suggest that either alternative mechanisms lead to inactivation of the PTEN gene or that other tumor-suppressor genes at chromosome 10 are implicated in the development of MCC.
默克尔细胞癌（MCC）是一种罕见的、具有高度转移性的神经外胚层起源的皮肤肿瘤。该疾病与小细胞肺癌（SCLC）具有临床和组织病理学特征。MCC发生和肿瘤进展的遗传机制尚不清楚。我们最近通过比较基因组杂交（CGH）表明，MCC中的染色体异常模式类似于SCLC。最常观察到的缺失之一涉及整个10号染色体或10号染色体长臂的部分缺失（33%的检测MCC病例）。PTEN肿瘤抑制基因已定位到10q23.3，并被证明在包括SCLC在内的多种人类癌症中发生突变。在包括考登病在内的家族性易感癌症综合征中已观察到种系PTEN突变。有趣的是，已有报道考登综合征与默克尔细胞癌之间存在关联。为了研究PTEN在MCC肿瘤发生中的可能作用，对来自23例MCC患者的26个MCC肿瘤样本进行了10q23区域的杂合性缺失（LOH）分析。在21个（43%）有信息的MCC肿瘤样本中的9个[18个（39%）MCC患者中的7个]中，PTEN基因座被删除。尽管10q23处的LOH频率很高，但PTEN基因的突变和纯合缺失筛查仅发现一个肿瘤有一个无义突变，另一个肿瘤有外显子9的纯合缺失。这些数据表明，要么是其他机制导致PTEN基因失活，要么是10号染色体上的其他肿瘤抑制基因与MCC的发生有关。
