Gandolfi Greta, Longo Caterina, Moscarella Elvira, Zalaudek Iris, Sancisi Valentina, Raucci Margherita, Manzotti Gloria, Gugnoni Mila, Piana Simonetta, Argenziano Giuseppe, Ciarrocchi Alessia
Laboratory of Translational Research, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy.
Skin Cancer Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
Pigment Cell Melanoma Res. 2016 Mar;29(2):163-75. doi: 10.1111/pcmr.12436. Epub 2016 Jan 12.
Recent evidence indicates that melanoma comprises distinct types of tumors and suggests that specific morphological features may help predict its clinical behavior. Using a SNP-array approach, we quantified chromosomal copy number alterations (CNA) across the whole genome in 41 primary melanomas and found a high degree of heterogeneity in their genomic asset. Association analysis correlating the number and relative length of CNA with clinical, morphological, and dermoscopic attributes of melanoma revealed that features of aggressiveness were strongly linked to the overall amount of genomic damage. Furthermore, we observed that melanoma progression and survival were mainly affected by a low number of large chromosome losses and a high number of small gains. We identified the alterations most frequently associated with aggressive melanoma, and by integrating our data with publicly available gene expression profiles, we identified five genes which expression was found to be necessary for melanoma cells proliferation. In conclusion, this work provides new evidence that the phenotypic heterogeneity of melanoma reflects a parallel genetic diversity and lays the basis to define novel strategies for a more precise prognostic stratification of patients.
最近的证据表明，黑色素瘤由不同类型的肿瘤组成，并表明特定的形态学特征可能有助于预测其临床行为。我们采用单核苷酸多态性阵列（SNP-array）方法，对41例原发性黑色素瘤的全基因组染色体拷贝数改变（CNA）进行了定量分析，发现其基因组特征存在高度异质性。将CNA的数量和相对长度与黑色素瘤的临床、形态学和皮肤镜特征进行关联分析，结果显示侵袭性特征与基因组损伤的总量密切相关。此外，我们观察到黑色素瘤的进展和生存主要受少量大染色体缺失和大量小染色体增加的影响。我们确定了与侵袭性黑色素瘤最常相关的改变，并通过将我们的数据与公开可用的基因表达谱相结合，确定了五个基因，其表达被发现是黑色素瘤细胞增殖所必需的。总之，这项工作提供了新的证据，表明黑色素瘤的表型异质性反映了平行的遗传多样性，并为定义更精确的患者预后分层新策略奠定了基础。
