Genomic characterization of rare molecular subclasses of hepatocellular carcinoma.
Genomic characterization of rare molecular subclasses of hepatocellular carcinoma.
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DOI：
10.1038/s42003-021-02674-1
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发表时间：
2021-10-04
影响因子：
5.9
通讯作者：
Hoadley KA
中科院分区：
文献类型：
--
作者：
Damrauer JS;Smith MA;Walter V;Thennavan A;Mose LE;Selitsky SR;Hoadley KA
原发性肝癌，包括胆管癌（CCA）和肝细胞癌（HCC），是世界范围内癌症死亡的第二大原因。我们的目标是从基因组学上描述罕见的HCC亚类，以深入了解疾病生物学。利用癌症基因组图谱（TCGA）对CCA（n = 36）和HCC（n = 275）进行联合分析，我们整合了多个基因组平台，以评估转录谱、突变特征和拷贝数模式，从而揭示潜在的病因学和谱系特异性模式。我们鉴定了两种与典型HCC肿瘤不同的分子类型。第一种是CCA样，尽管在组织学上与HCC无法区分，但具有CCA突变（IDH1，BAP 1），突变特征和转录模式（SOX 9，KRT 19）的富集。然而，CCA样保留了与HCC相似的拷贝数景观，表明肝细胞谱系。第二种，胚样，富含TP53突变，HBV感染，暴露相关的突变特征，转录类似于肝母细胞。虽然这些亚类在分子上是不同的，但与经典的HCC肿瘤相比，它们的无进展生存率都更差，但临床治疗相同。CCA样和母细胞样亚类的鉴定和表征推进了我们对HCC的认识，并且代表了对鉴定类别特异性生物标志物和靶向治疗的迫切需要。Jeffrey Damrauer、Markia Smith等人基于分子数据的综合分析，使用来自胆管癌（CCA）和肝细胞癌（HCC）的现有数据集来表征与原型HCC肿瘤不同的两个HCC子集。这两类癌症在拷贝数、基因表达和突变特征方面与HCC不同，并且表现出更差的无进展生存期，这突出了识别类别特异性生物标志物和开发针对这些癌症形式的靶向治疗的必要性。
Primary liver cancer, consisting of both cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC), is the second leading cause of cancer deaths worldwide. Our goal is to genomically characterize rare HCC subclasses to provide insight into disease biology. Leveraging The Cancer Genome Atlas (TCGA) to perform a combined analysis of CCA (n = 36) and HCC (n = 275), we integrated multiple genomic platforms, to assess transcriptional profiles, mutational signatures, and copy number patterns to uncover underlying etiology and linage specific patterns. We identified two molecular classes distinct from prototypical HCC tumors. The first, CCA-Like, although histologically indistinguishable from HCC, had enrichment of CCA mutations (IDH1, BAP1), mutational signatures, and transcriptional patterns (SOX9, KRT19). CCA-Like, however, retained a copy number landscape similar to HCC, suggesting a hepatocellular linage. The second, Blast-Like, is enriched in TP53 mutations, HBV infection, exposure related mutational signatures and transcriptionally similar to hepatoblasts. Although these subclasses are molecularly distinct, they both have a worse progression-free survival compared to classical HCC tumors, yet are clinically treated the same. The identification of and characterization of CCA-Like and Blast-Like subclasses advance our knowledge of HCC as well as represents an urgent need for the identification of class specific biomarkers and targeted therapy. Jeffrey Damrauer, Markia Smith et al. used existing datasets from cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) to characterize two subsets of HCC distinct from prototypical HCC tumors, based on comprehensive analysis of molecular data. The two classes differed from HCC by their copy number, gene expression and mutational signature and exhibited worse progression free survival, highlighting the need to identify class-specific biomarkers and develop targeted therapies for these forms of cancer.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
DOI：
10.1186/1476-5926-9-9
发表时间：
2010-12-02
期刊：
Comparative hepatology
影响因子：
--
作者：
Limaye PB;Bowen WC;Orr A;Apte UM;Michalopoulos GK
通讯作者：
Michalopoulos GK
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu;Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
11.2
作者：
Hoshida Y;Nijman SM;Kobayashi M;Chan JA;Brunet JP;Chiang DY;Villanueva A;Newell P;Ikeda K;Hashimoto M;Watanabe G;Gabriel S;Friedman SL;Kumada H;Llovet JM;Golub TR
通讯作者：
Golub TR
影响因子：
64.5
作者：
Liu J;Lichtenberg T;Hoadley KA;Poisson LM;Lazar AJ;Cherniack AD;Kovatich AJ;Benz CC;Levine DA;Lee AV;Omberg L;Wolf DM;Shriver CD;Thorsson V;Cancer Genome Atlas Research Network;Hu H
通讯作者：
Hu H