Identification_of_mutations_in_mucosal_melanoma. Identification_of_mutations_in_mucosal_melanoma

Primary mucosal melanomas (MMs) arise from melanocytes located in mucosal membranes lining the respiratory, gastrointestinal and urogenital tracts. MMs frequently present late and have a poor prognosis; the 5-year survival rate is only 14%. MM makes up only ~1.4% of all melanomas and it is this rarity that makes knowledge of the genetic changes that contribute to its pathogenesis limited to a small number of exome/genome studies and other targeted studies. Thus to investigate the somatic alterations and mutation spectra in MM genomes, we have extracted genomic DNA from formalin-fixed, paraffin-embedded (FFPE) canine oral melanomas, and their metastatic counterparts, and subjected them to targeted exome sequencing. which are of mucosal origin and will use this for targeted exome sequencing. Given the propensity of MM to metastasize, we will also be sequencing metastatic MM lesions; primary and metastatic lesions from the same dog represent an excellent opportunity to identify potential drivers of metastasis in MM. Finally we will sequence ‘normal’ DNA from the same dog, where possible, to.

原发性黏膜黑色素瘤（Primary mucosal melanomas, MMs）起源于分布于呼吸道、消化道及泌尿生殖道黏膜上皮的黑色素细胞。该类肿瘤往往确诊时已属晚期，预后极差，5年生存率仅为14%。黏膜黑色素瘤仅占所有黑色素瘤的约1.4%，正是由于其发病率极低，目前对其发病相关遗传改变的认知仅局限于少量外显子组/基因组研究及其他靶向研究中。为探究黏膜黑色素瘤基因组中的体细胞变异与突变谱，本研究从福尔马林固定石蜡包埋（Formalin-fixed paraffin-embedded, FFPE）的犬口腔黑色素瘤及其转移灶样本中提取了基因组DNA，并对其进行靶向外显子组测序；上述样本均为黏膜起源，本研究将依托该测序数据开展后续分析。鉴于黏膜黑色素瘤易发生转移的特性，本研究还将对转移灶样本进行测序；来自同一犬只的原发灶与转移灶样本，为识别黏膜黑色素瘤转移潜在驱动因素提供了绝佳研究契机。最后，在可行的前提下，本研究还将对同一犬只的正常组织DNA进行测序，以