The mutational landscape of adenoid cystic carcinoma.
The mutational landscape of adenoid cystic carcinoma.
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DOI：
10.1038/ng.2643
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发表时间：
2013-07
期刊：
影响因子：
30.8
通讯作者：
Chan, Timothy A.
中科院分区：
文献类型：
--
作者：
Ho, Allen S.;Kannan, Kasthuri;Roy, David M.;Morris, Luc G. T.;Ganly, Ian;Katabi, Nora;Ramaswami, Deepa;Walsh, Logan A.;Eng, Stephanie;Huse, Jason T.;Zhang, Jianan;Dolgalev, Igor;Huberman, Kety;Heguy, Adriana;Viale, Agnes;Drobnjak, Marija;Leversha, Margaret A.;Rice, Christine E.;Singh, Bhuvanesh;Iyer, N. Gopalakrishna;Leemans, C. Rene;Bloemena, Elisabeth;Ferris, Robert L.;Seethala, Raja R.;Gross, Benjamin E.;Liang, Yupu;Sinha, Rileen;Peng, Luke;Raphael, Benjamin J.;Turcan, Sevin;Gong, Yongxing;Schultz, Nikolaus;Kim, Seungwon;Chiosea, Simion;Shah, Jatin P.;Sander, Chris;Lee, William;Chan, Timothy A.
腺样囊性癌是人类最神秘的恶性肿瘤之一。这些侵袭性唾液腺癌经常复发和转移，尽管明确的治疗，没有已知的有效化疗方案。在这里，我们确定了ACC突变景观，并报告了60个ACC肿瘤/正常对的外显子组或全基因组序列。这些分析揭示了低外显子体细胞突变率（0.31非沉默事件/兆碱基）和广泛的突变多样性。有趣的是，突变选择性地涉及染色质状态调节因子，如SMARCA 2，CREBBP和KDM 6A，表明ACC肿瘤发生中的异常表观遗传调节。DNA损伤和蛋白激酶A信号传导的核心基因突变也涉及这些过程。我们观察到MYB-NFIB易位和MYB相关基因的体细胞突变，巩固这些畸变作为关键事件。最后，我们确定了FGF/IGF/PI 3 K通路中的复发性突变，这些突变可能为治疗提供新的途径（30%）。总的来说，我们的观察为理解和探索ACC的新治疗方法奠定了分子基础。
Adenoid cystic carcinomas (ACCs) are among the most enigmatic of human malignancies. These aggressive salivary cancers frequently recur and metastasize despite definitive treatment, with no known effective chemotherapy regimen. Here, we determined the ACC mutational landscape and report the exome or whole genome sequences of 60 ACC tumor/normal pairs. These analyses revealed a low exonic somatic mutation rate (0.31 non-silent events/megabase) and wide mutational diversity. Interestingly, mutations selectively involved chromatin state regulators, such as SMARCA2, CREBBP, and KDM6A, suggesting aberrant epigenetic regulation in ACC oncogenesis. Mutations in genes central to DNA damage and protein kinase A signaling also implicate these processes. We observed MYB-NFIB translocations and somatic mutations in MYB-associated genes, solidifying these aberrations as critical events. Lastly, we identified recurrent mutations in the FGF/IGF/PI3K pathway that may potentially offer new avenues for therapy (30%). Collectively, our observations establish a molecular foundation for understanding and exploring new treatments for ACC.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
50.3
作者：
Figueroa ME;Abdel-Wahab O;Lu C;Ward PS;Patel J;Shih A;Li Y;Bhagwat N;Vasanthakumar A;Fernandez HF;Tallman MS;Sun Z;Wolniak K;Peeters JK;Liu W;Choe SE;Fantin VR;Paietta E;Löwenberg B;Licht JD;Godley LA;Delwel R;Valk PJ;Thompson CB;Levine RL;Melnick A
通讯作者：
Melnick A
影响因子：
45.3
作者：
Agulnik, Mark;Cohen, Ezra W. E.;Siu, Lillian L.
通讯作者：
Siu, Lillian L.
影响因子：
11.2
作者：
Dey, Julien H.;Bianchi, Fabrizio;Hynes, Nancy E.
通讯作者：
Hynes, Nancy E.
影响因子：
11.5
作者：
Brooks, A. Nigel;Kilgour, Elaine;Smith, Paul D.
通讯作者：
Smith, Paul D.