Specific human endogenous retroviruses predict metastatic potential in uveal melanoma.
Specific human endogenous retroviruses predict metastatic potential in uveal melanoma.
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DOI：
10.1172/jci.insight.147172
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发表时间：
2022-05-09
期刊：
影响因子：
8
通讯作者：
Nixon, Douglas F.
中科院分区：
文献类型：
--
作者：
Bendall, Matthew L.;Francis, Jasmine H.;Shoushtari, Alexander N.;Nixon, Douglas F.
葡萄膜黑色素瘤 (UM) 是一种独特的疾病，原发性 UM 患者根据发生转移的风险进行了良好分层，但一旦发生转移，有效的治疗方法有限。迫切需要更好地了解 UM 的独特分子发病机制和高转移风险患者的特征，以确定可用于免疫治疗的新抗原靶标，并开发可有效针对这种致命转变的新治疗策略。 UM 分子发病机制和新抗原靶标的一个重要且被忽视的领域来自人内源性逆转录病毒 (HERV)。我们研究了原发性 UM 中的 HERV 表达情况，发现肿瘤被分为 4 个基于 HERV 的子集，这些子集提供了风险结果的清晰描述，并支持通过其他分子指标识别的亚型。特定的 HERV 位点与葡萄膜黑色素瘤转移的风险相关，并可能为这一过程提供机制见解，包括 3 号和 8 号染色体上 HERV 的失调。由 17 个位点组成的 HERV 特征足以根据亚型对肿瘤进行分类，准确率超过 95%，其中至少有 1 个具有编码潜力的基因间 HERV (HERVE_Xp11.23)，可以代表潜在的 HERV E 靶点免疫疗法。
Uveal melanoma (UM) is a unique disease in that patients with primary UM are well stratified based on their risk of developing metastasis, yet there are limited effective treatments once metastases occur. There is an urgent need to better understand the distinct molecular pathogenesis of UM and the characteristics of patients at high risk for metastasis to identify neoantigenic targets that can be used in immunotherapy and to develop novel therapeutic strategies that may effectively target this lethal transition. An important and overlooked area of molecular pathogenesis and neoantigenic targets in UM comes from human endogenous retroviruses (HERVs). We investigated the HERV expression landscape in primary UM and found that tumors were stratified into 4 HERV-based subsets that provide clear delineation of risk outcome and support subtypes identified by other molecular indicators. Specific HERV loci are associated with the risk of uveal melanoma metastasis and may offer mechanistic insights into this process, including dysregulation of HERVs on chromosomes 3 and 8. A HERV signature composed of 17 loci was sufficient to classify tumors according to subtype with greater than 95% accuracy, including at least 1 intergenic HERV with coding potential (HERVE_Xp11.23) that could represent a potential HERV E target for immunotherapy.
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影响因子：
5.2
作者：
Balestrieri E;Argaw-Denboba A;Gambacurta A;Cipriani C;Bei R;Serafino A;Sinibaldi-Vallebona P;Matteucci C
通讯作者：
Matteucci C
影响因子：
4.7
作者：
Agoni L;Guha C;Lenz J
通讯作者：
Lenz J
影响因子：
8
作者：
Cherkasova, E.;Malinzak, E.;Rao, S.;Takahashi, Y.;Senchenko, V. N.;Kudryavtseva, A. V.;Nickerson, M. L.;Merino, M.;Hong, J. A.;Schrump, D. S.;Srinivasan, R.;Linehan, W. M.;Tian, X.;Lerman, M. I.;Childs, R. W.
通讯作者：
Childs, R. W.
影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
通讯作者：
Noushmehr H
影响因子：
5.2
作者：
Curty G;Menezes AN;Brant AC;de Mulder Rougvie M;Moreira MÂM;Soares MA
通讯作者：
Soares MA