Medical Genetics, Department of Molecular Medicine, San Camillo-Forlanini Hospital, Sapienza University, Circonvallazione Gianicolense, 87, 00152, Rome, Italy.
Fam Cancer. 2012 Jun;11(2):201-8. doi: 10.1007/s10689-011-9502-6.
MicroRNAs are small non-coding RNAs, which inhibit expression of specific target genes at the post-transcriptional level and are often misregulated in human cancer. Among them, miR-34a is considered a tumor suppressor with a hypothetical role in melanoma tumorigenesis. In this work, 62 Italian index patients with familial melanoma and negative for CDKN2A/CDK4 screening were investigated for miR-34a germline mutations. Eight novel miR-34a sequence variants were identified at both the heterozygous (c.+259G>A, c.+424G>A, c.+1465C>T, c.+1769C>T, c.+2456T>G, c.+2603C>T, c.+2972T>A, c.+3069T>C) and homozygous (c.+424G>A, c.+1465C>T, c.+1769C>T) states. Molecular screening identified all nucleotide changes in a healthy population of 150 controls and demonstrated that they are common polymorphisms. However, statistically significant differences of allele and genotype frequencies were detected for c.+1465C>T and c.+1769C>T, and borderline values for c.+2456T>G. By stratifying patients by relevant clinical features (presence/absence of multiple primary melanoma, Breslow's thickness, phototype and number of nevi), no significant findings were noted except for an association between the c.+424G>A (heterozygous individual GA) and multiple primary melanoma and phototype III-IV. Our preliminary study suggests that miR-34a, although having a role in late tumorigenesis, does not contribute to the inherited susceptibility to cutaneous melanoma. A function as phenotypic modulator in familial melanoma cannot be excluded.
微小 RNA 是小的非编码 RNA，它们在后转录水平上抑制特定靶基因的表达，并且在人类癌症中经常失调。其中，miR-34a 被认为是一种肿瘤抑制因子，在黑色素瘤肿瘤发生中具有假设作用。在这项工作中，对 62 名意大利家族性黑色素瘤索引患者进行了研究，这些患者为 CDKN2A/CDK4 筛查阴性，并对其 miR-34a 种系突变进行了研究。在杂合状态（c.+259G>A、c.+424G>A、c.+1465C>T、c.+1769C>T、c.+2456T>G、c.+2603C>T、c.+2972T>A、c.+3069T>C）和纯合状态（c.+424G>A、c.+1465C>T、c.+1769C>T）下鉴定出了 8 个新的 miR-34a 序列变体。分子筛查在 150 名健康对照人群中发现了所有核苷酸变化，并证明它们是常见的多态性。然而，c.+1465C>T 和 c.+1769C>T 的等位基因和基因型频率以及 c.+2456T>G 的边界值存在统计学显著差异。通过对相关临床特征（多发性原发性黑色素瘤、Breslow 厚度、光型和痣的数量）进行分层的患者进行分析，除了 c.+424G>A（杂合个体 GA）与多发性原发性黑色素瘤和光型 III-IV 之间存在关联外，没有发现显著的发现。我们的初步研究表明，miR-34a 虽然在晚期肿瘤发生中起作用，但不会导致皮肤黑色素瘤的遗传易感性。不能排除其在家族性黑色素瘤中作为表型调节剂的作用。
