Metastatic and recurrent adrenocortical cancer is not defined by its genomic landscape.
Metastatic and recurrent adrenocortical cancer is not defined by its genomic landscape.
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转移性和复发性肾上腺皮质癌并不由其基因组景观定义。
DOI：
10.1186/s12920-020-00809-7
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发表时间：
2020-11-04
影响因子：
2.7
通讯作者：
Dean M
中科院分区：
文献类型：
--
作者：
Fojo T;Huff L;Litman T;Im K;Edgerly M;Del Rivero J;Pittaluga S;Merino M;Bates SE;Dean M
肾上腺皮质癌（ACC）是一种罕见的肾上腺皮质肿瘤，通常具有侵袭性，中位总生存期为14-17个月。我们询问晚期或转移性ACC患者的肿瘤是否会提供可能在疾病进展或更具侵袭性的疾病生物学中起关键作用的推定基因的线索。 我们对来自43名患者（30名女性）和42名来自转移部位的ACC进行了全面的基因组和表达分析，包括深度测序、拷贝数分析、mRNA表达和microRNA阵列。拷贝数的增加和减少与以前报道的ACC相似，我们发现突变率中位数为3.38/Mb。突变特征的特征在于C > T、C > A和T > C转换的优势。只有癌症基因TP 53（26%）和β-连环蛋白（CTNNB 1，14%）在超过10%的样本中发生突变。TCGA鉴定的推定癌症基因MEN 1和PRKAR 1A的频率较低，分别为4.7%和2.3%。大多数突变发生在与癌症病因或维持无关的基因中。具体来说，在超过9%的样本中突变的38个基因中，只有4个在576个COSMIC癌症基因普查（CCGC）的第1层中。因此，82%的基因突变可能在ACC的病因学或生物学中没有作用;而其他18%的作用，如果有的话，仍有待证明。最后，ACC中38个最常突变基因的转录本长度在统计学上长于所有编码基因的平均值，这就提出了转录本长度是否部分决定突变概率的问题。我们的结论是，晚期和转移性肿瘤的突变和表达谱与新诊断患者的突变和表达谱非常相似，几乎没有基因组畸变来解释生物学差异。相对较低的突变率，几个主要的致癌驱动程序，并在几个表观遗传调节因子的功能突变的损失，ACC的表观遗传基础可能被假定，并作为未来研究的基础。
Adrenocortical carcinoma (ACC) is a rare, often-aggressive neoplasm of the adrenal cortex, with a 14–17 month median overall survival. We asked whether tumors from patients with advanced or metastatic ACC would offer clues as to putative genes that might have critical roles in disease progression or in more aggressive disease biology. We conducted comprehensive genomic and expression analyses of ACCs from 43 patients, 30 female, and 42 from metastatic sites, including deep sequencing, copy number analysis, mRNA expression and microRNA arrays. Copy number gains and losses were similar to that previously reported for ACC. We identified a median mutation rate of 3.38 per megabase (Mb). The mutational signature was characterized by a predominance of C > T, C > A and T > C transitions. Only cancer genes TP53 (26%) and beta-catenin (CTNNB1, 14%) were mutated in more than 10% of samples. The TCGA-identified putative cancer genes MEN1 and PRKAR1A were found in low frequency—4.7 and 2.3%, respectively. The majority of the mutations were in genes not implicated in the etiology or maintenance of cancer. Specifically, amongst the 38 genes that were mutated in more than 9% of samples, only four were represented in Tier 1 of the 576 COSMIC Cancer Gene Census (CCGC). Thus, 82% of genes found to have mutations likely have no role in the etiology or biology of ACC; while the role of the other 18%, if any, remains to be proven. Finally, the transcript length for the 38 most frequently mutated genes in ACC is statistically longer than the average of all coding genes, raising the question of whether transcript length in part determined mutation probability. We conclude that the mutational and expression profiles of advanced and metastatic tumors are very similar to those from newly diagnosed patients—with very little in the way of genomic aberration to explain differences in biology. With relatively low mutation rates, few major oncogenic drivers, and loss of function mutations in several epigenetic regulators, an epigenetic basis for ACC may be postulated and serve as the basis for future studies.
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影响因子：
50.3
作者：
Hellmann MD;Callahan MK;Awad MM;Calvo E;Ascierto PA;Atmaca A;Rizvi NA;Hirsch FR;Selvaggi G;Szustakowski JD;Sasson A;Golhar R;Vitazka P;Chang H;Geese WJ;Antonia SJ
通讯作者：
Antonia SJ
DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.8
作者：
Barreau, Olivia;Assie, Guillaume;Bertherat, Jerome
通讯作者：
Bertherat, Jerome
影响因子：
45.3
作者：
de Reynies, Aurelien;Assie, Guillaume;Bertherat, Jerome
通讯作者：
Bertherat, Jerome
影响因子：
5.8
作者：
Chapman, Audrey;Durand, Julien;Bourdeau, Isabelle
通讯作者：
Bourdeau, Isabelle