Characterization of genetics in patients with mucosal melanoma treated with immune checkpoint blockade.
Characterization of genetics in patients with mucosal melanoma treated with immune checkpoint blockade.
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DOI：
10.1002/cam4.3789
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发表时间：
2021-04
期刊：
影响因子：
4
通讯作者：
Hodi FS
中科院分区：
文献类型：
--
作者：
Buchbinder EI;Weirather JL;Manos M;Quattrochi BJ;Sholl LM;Brennick RC;Bowling P;Bailey N;Magarace L;Ott PA;Haq R;Izar B;Giobbie-Hurder A;Hodi FS
黏膜黑色素瘤是一种罕见的黑色素瘤类型，它起源于黏膜中的黑素细胞，可通过免疫检查点阻断（ICB）进行有效治疗。然而，黏膜黑色素瘤的应答率低于皮肤黑色素瘤。
2011年至2019年3月期间，对在丹娜 - 法伯癌症研究所就诊的所有黏膜黑色素瘤患者的肿瘤进行了多达447个基因的靶向测序（OncoPanel）。
我们共确定了46名接受ICB治疗且有肿瘤基因型和ICB应答数据的患者。在这组患者中，16人（35%）对其一线ICB治疗有持久的临床获益（DCB）。平均突变负荷/兆碱基为6.23，且与肿瘤对ICB的应答无关。具有KIT异常的患者与野生型KIT患者相比，有更高的DCB率（71%对28%），但这未发现有统计学意义。为作比较，我们分析了另外50个黏膜黑色素瘤肿瘤和189个皮肤黑色素瘤肿瘤的肿瘤基因型。黏膜黑色素瘤中最常见的突变在SF3B1（27%）、KIT（18%）和NF1（17%），这一模式与皮肤黑色素瘤不同。此外，根据黏膜黑色素瘤的起源部位观察到了基因差异。
我们的研究结果探讨了接受ICB治疗的黏膜黑色素瘤患者的应答临床特征，并表明低突变负荷与应答无关。此外，所检测的基因异常与对ICB的应答之间缺乏显著关联，这表明需要在该患者群体中进一步探索。
黏膜黑色素瘤是一种罕见的黑色素瘤，它起源于鼻腔、肠道或阴道内的黏膜。它可以通过针对免疫检查点的新型免疫疗法进行治疗，且取得了一定的成功，但并非所有患者对这些疗法都有应答。这项研究检查了黏膜黑色素瘤内的基因变化，以寻找可能有助于预测谁会对免疫疗法有良好应答以及谁不会应答的模式。观察到了一些有趣的趋势，但需要更多的工作来确定与治疗相关的黏膜黑色素瘤基因突变。
Mucosal melanoma is a rare form of melanoma which arises from melanocytes in the mucosal membranes and can be effectively treated with immune checkpoint blockade (ICB). However, response rates in mucosal melanoma are lower than those observed for cutaneous melanomas. Targeted sequencing of up to 447 genes (OncoPanel) was performed on tumors from all mucosal melanoma patients seen at the Dana‐Farber Cancer Institute from 2011 until March 2019. We identified a total of 46 patients who received ICB with both tumor‐genotype and ICB response data available. Within this cohort of patients, 16 (35%) had durable clinical benefit (DCB) to their first line of ICB. The average mutational burden/megabase was 6.23 and did not correlate with tumor response to ICB. Patients with KIT aberrations had a higher DCB rate compared with patients with wildtype KIT (71 vs. 28%), but this was not found to be statistically significant. For comparison, we analyzed tumor genotypes from an additional 50 mucosal melanoma tumors and 189 cutaneous melanoma tumors. The most frequent mutations in mucosal melanoma were in SF3B1 (27%), KIT (18%), and NF1 (17%), a pattern that is distinct from cutaneous melanomas. In addition, there were genetic differences observed based upon the site of origin of the mucosal melanoma. Our findings explore clinical features of response in patients with mucosal melanoma treated with ICB and demonstrate a low mutational burden that does not correlate with response. In addition, the lack of significant association between the genetic aberrations tested and response to ICB indicates the need for further exploration in this patient population. Mucosal melanoma is a rare form of melanoma that arises from mucosal membranes within the nose, intestines or vaginal cavity. It can be treated with new immunotherapies that target immune checkpoints with some success but not all patients respond to these therapies. This study examines the genetic changes within mucosal melanoma to look for patterns that may help predict who will respond well to immunotherapy and who will not respond. Some interesting trends were observed but more work is needed to determine genetic mutations in mucosal melanoma that are associated with treatment.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
6.2
作者：
Shoushtari, Alexander N.;Munhoz, Rodrigo R.;Kuk, Deborah;Ott, Patrick A.;Johnson, Douglas B.;Tsai, Katy K.;Rapisuwon, Suthee;Eroglu, Zeynep;Sullivan, Ryan J.;Luke, Jason J.;Gangadhar, Tara C.;Salama, April K. S.;Clark, Varina;Burias, Clare;Puzanov, Igor;Atkins, Michael B.;Algazi, Alain P.;Ribas, Antoni;Wolchok, Jedd D.;Postow, Michael A.
通讯作者：
Postow, Michael A.
影响因子：
8.1
作者：
Decatur CL;Ong E;Garg N;Anbunathan H;Bowcock AM;Field MG;Harbour JW
通讯作者：
Harbour JW
影响因子：
30.8
作者：
Harbour, J. William;Roberson, Elisha D. O.;Anbunathan, Hima;Onken, Michael D.;Worley, Lori A.;Bowcock, Anne M.
通讯作者：
Bowcock, Anne M.
影响因子：
8.4
作者：
Heppt, Markus V.;Roesch, Alexander;Berking, Carola
通讯作者：
Berking, Carola