Beyond Traditional Morphological Characterization of Lung Neuroendocrine Neoplasms: In Silico Study of Next-Generation Sequencing Mutations Analysis across the Four World Health Organization Defined Groups.
Beyond Traditional Morphological Characterization of Lung Neuroendocrine Neoplasms: In Silico Study of Next-Generation Sequencing Mutations Analysis across the Four World Health Organization Defined Groups.
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DOI：
10.3390/cancers12102753
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发表时间：
2020-09-24
期刊：
影响因子：
5.2
通讯作者：
Milione M
中科院分区：
文献类型：
--
作者：
Centonze G;Biganzoli D;Prinzi N;Pusceddu S;Mangogna A;Tamborini E;Perrone F;Busico A;Lagano V;Cattaneo L;Sozzi G;Roz L;Biganzoli E;Milione M
世界卫生组织2015年提出的肺神经内分泌肿瘤（LNEN）分类未提供适当的预后和治疗适应症。事实上，基于下一代测序的高通量分子分析确定了与不同基因组特征相关的新分子亚组，这可能为替代治疗方法铺平道路。目前的审查，加上在计算机分子分析，可以显示当前的基因组改变在实际LNENS组的状态。有趣的是，我们的手稿表明，分子新颖性可以提高LNEN的治疗效果。更详细地说，我们报道了LNENS之间的基因改变和突变率的差异，证实了染色质重塑基因和肿瘤抑制基因TP 53-RB 1的不同突变率所赋予的中心致病作用。总之，我们的研究结果强调，需要进一步的分子层来提高LNENs药物治疗的疗效。肺神经内分泌肿瘤（LNEN）是一种罕见的异质性肺肿瘤。LNEN的发病率在过去30年中急剧增加。目前世界卫生组织LNEN分类（WHO 2015）根据其形态、坏死量和有丝分裂计数将LNEN分为四个预后类别：典型类癌（TC）、恶性类癌（AC）、大细胞神经内分泌癌（LCNEC）和小细胞肺癌（SCLC）。目前，由于其罕见性和生物学异质性，对于最佳治疗方法仍然没有达成共识。新一代测序分析表明，WHO 2015 LNEN类别也可以通过特定的分子改变来表征：在TC和AC中经常检测到涉及染色质重塑的频繁突变基因，通常以低突变负荷（MB）为特征;否则，在LCNEC和SCLC中通常检测到TP 53和RB 1肿瘤抑制基因改变和高MB。我们提供了关于每个WHO 2015 LNENs类别中基因突变的概述，以报告当前LNENs突变状态，作为更好地了解其临床结果和推动医学治疗的潜在工具。
Lung neuroendocrine neoplasms (LNENs) classes, as proposed by the World Health Organization 2015, do not provide properly prognostic and therapeutic indications. In fact, high-throughput molecular analysis, based on next-generation sequencing, identified novel molecular subgroups, associated with different genomic signatures, that could pave the way for alternative therapeutic approaches. The present review, coupled with in silico molecular analysis, could show the current genomic alterations state in actual LNENS groups. Interestingly our manuscript suggests that the molecular novelties could improve the LNENs therapeutics efficacy. In more detail, we reported the differences of gene alterations and mutational rate between LNENS, confirming the central pathogenetic role given by a different mutational rate in chromatin remodeling genes and tumor suppressors TP53-RB1. In conclusion, our results underlined that a further molecular layer is needed to improve the efficacy of LNENs medical treatment. Lung neuroendocrine neoplasms (LNENs) represent a rare and heterogeneous population of lung tumors. LNENs incidence rate has increased dramatically over the past 30 years. The current World Health Organization LNENs classification (WHO 2015), distinguished four LNENs prognostic categories, according to their morphology, necrosis amount and mitotic count: typical carcinoid (TC), atypical-carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC). At present, due to their rarity and biological heterogeneity there is still no consensus on the best therapeutic approach. Next-generation-sequencing analysis showed that WHO 2015 LNENs classes, could be characterized also by specific molecular alterations: frequently mutated genes involving chromatin remodeling and generally characterized by low mutational burden (MB) are frequently detected in both TC and AC; otherwise, TP53 and RB1 tumor suppressor genes alterations and high MB are usually detected in LCNEC and SCLC. We provide an overview concerning gene mutations in each WHO 2015 LNENs class in order to report the current LNENs mutational status as potential tool to better understand their clinical outcome and to drive medical treatment.
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影响因子：
4.1
作者：
Milione, Massimo;Maisonneuve, Patrick;Capella, Carlo
通讯作者：
Capella, Carlo
影响因子：
11.2
作者：
Laddha, Saurabh V.;da Silva, Edaise M.;Chan, Chang S.
通讯作者：
Chan, Chang S.
影响因子：
16.6
作者：
Fernandez-Cuesta, Lynnette;Peifer, Martin;Lu, Xin;Sun, Ruping;Ozretic, Luka;Seidel, Danila;Zander, Thomas;Leenders, Frauke;George, Julie;Mueller, Christian;Dahmen, Ilona;Pinther, Berit;Bosco, Graziella;Konrad, Kathryn;Altmueller, Janine;Nuernberg, Peter;Achter, Viktor;Lang, Ulrich;Schneider, Peter M.;Bogus, Magdalena;Soltermann, Alex;Brustugun, Odd Terje;Helland, Aslaug;Solberg, Steinar;Lund-Iversen, Marius;Ansen, Sascha;Stoelben, Erich;Wright, Gavin M.;Russell, Prudence;Wainer, Zoe;Solomon, Benjamin;Field, John K.;Hyde, Russell;Davies, Michael P. A.;Heukamp, Lukas C.;Petersen, Iver;Perner, Sven;Lovly, Christine M.;Cappuzzo, Federico;Travis, William D.;Wolf, Juergen;Vingron, Martin;Brambilla, Elisabeth;Haas, Stefan A.;Buettner, Reinhard;Thomas, Roman K.
通讯作者：
Thomas, Roman K.
影响因子：
16.6
作者：
George J;Walter V;Peifer M;Alexandrov LB;Seidel D;Leenders F;Maas L;Müller C;Dahmen I;Delhomme TM;Ardin M;Leblay N;Byrnes G;Sun R;De Reynies A;McLeer-Florin A;Bosco G;Malchers F;Menon R;Altmüller J;Becker C;Nürnberg P;Achter V;Lang U;Schneider PM;Bogus M;Soloway MG;Wilkerson MD;Cun Y;McKay JD;Moro-Sibilot D;Brambilla CG;Lantuejoul S;Lemaitre N;Soltermann A;Weder W;Tischler V;Brustugun OT;Lund-Iversen M;Helland Å;Solberg S;Ansén S;Wright G;Solomon B;Roz L;Pastorino U;Petersen I;Clement JH;Sänger J;Wolf J;Vingron M;Zander T;Perner S;Travis WD;Haas SA;Olivier M;Foll M;Büttner R;Hayes DN;Brambilla E;Fernandez-Cuesta L;Thomas RK
通讯作者：
Thomas RK
DOI：
10.1016/j.neo.2017.09.002
发表时间：
2017-12
期刊：
Neoplasia (New York, N.Y.)
影响因子：
--
作者：
Oronsky B;Ma PC;Morgensztern D;Carter CA
通讯作者：
Carter CA