Clinical Next-Generation Sequencing Panels Reveal Molecular Differences Between Merkel Cell Polyomavirus-Negative Merkel Cell Carcinomas and Neuroendocrine Carcinomas

被引:5
|
作者
Hartsough, Emily [1 ,2 ]
Mino-Kenudson, Mari [1 ,2 ]
Lennerz, Jochen K. [1 ,2 ]
Dias-Santagata, Dora [1 ,2 ]
Hoang, Mai P. [1 ,2 ]
机构
[1] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA
[2] Harvard Med Sch, Boston, MA 02115 USA
关键词
Molecular analyses; Merkel cell carcinoma; Neuroendocrine carcinoma; Next-generation sequencing; Fusion analyses; UV signature; TMPRSS2-ERG GENE FUSION; LUNG-CARCINOMA; EML4-ALK REARRANGEMENT; MUTATIONAL LANDSCAPE; ALK-REARRANGEMENT; PARTIAL-RESPONSE; IDENTIFICATION; PULMONARY; ADENOCARCINOMA; CANCER;
D O I
10.1093/ajcp/aqac176
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Objectives We aim to determine molecular differences between Merkel cell polyomavirus (MCPyV)-negative Merkel cell carcinomas (MCCs) and neuroendocrine carcinomas (NECs). Methods Our study included 56 MCCs (28 MCPyV negative, 28 MCPyV positive) and 106 NECs (66 small cell NECs, 21 large cell NECs, and 19 poorly differentiated NECs) submitted for clinical molecular testing. Results APC, MAP3K1, NF1, PIK3CA, RB1, ROS1, and TSC1 mutations, in addition to high tumor mutational burden and UV signature, were frequently noted in MCPyV-negative MCC in comparison to small cell NEC and all NECs analyzed, while KRAS mutations were more frequently noted in large cell NEC and all NECs analyzed. Although not sensitive, the presence of either NF1 or PIK3CA is specific for MCPyV-negative MCC. The frequencies of KEAP1, STK11, and KRAS alterations were significantly higher in large cell NEC. Fusions were detected in 6.25% (6/96) of NECs yet in none of 45 analyzed MCCs. Conclusions High tumor mutational burden and UV signature, as well as the presence of NF1 and PIK3CA mutations, are supportive of MCPyV-negative MCC, whereas KEAP1, STK11, and KRAS mutations are supportive of NEC in the appropriate clinical context. Although rare, the presence of a gene fusion is supportive of NEC.
引用
收藏
页码:395 / 406
页数:12
相关论文
共 50 条
  • [31] Diagnostic accuracy of a panel of immunohistochemical and molecular markers to distinguish Merkel cell carcinoma from other neuroendocrine carcinomas
    Kervarrec, Thibault
    Tallet, Anne
    Miquelestorena-Standley, Elodie
    Houben, Roland
    Schrama, David
    Gambichler, Thilo
    Berthon, Patricia
    Le Corre, Yannick
    Hainaut-Wierzbicka, Ewa
    Aubin, Francois
    Bens, Guido
    Tabareau-Delalande, Flore
    Beneton, Nathalie
    Fromont, Gaelle
    Arbion, Flavie
    Leteurtre, Emmanuelle
    Touze, Antoine
    Samimi, Mahtab
    Guyetant, Serge
    MODERN PATHOLOGY, 2019, 32 (04) : 499 - 510
  • [32] PRIMARY NEUROENDOCRINE CARCINOMAS OF THE SKIN (MERKEL CELL TUMORS) - A CLINICAL, HISTOLOGIC, AND ULTRASTRUCTURAL-STUDY OF 13 CASES
    WICK, MR
    GOELLNER, JR
    SCHEITHAUER, BW
    THOMAS, JR
    SANCHEZ, NP
    SCHROETER, AL
    AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 1983, 79 (01) : 6 - 13
  • [33] Classifying the Unclassified Renal Cell Carcinomas Using Next-Generation Sequencing Genomic Profiling
    Kong, Qingnuan
    Zhou, Ming
    MODERN PATHOLOGY, 2019, 32
  • [34] Classifying the Unclassified Renal Cell Carcinomas Using Next-Generation Sequencing Genomic Profiling
    Kong, Qingnuan
    Zhou, Ming
    LABORATORY INVESTIGATION, 2019, 99
  • [35] Assessment of the Mutation Profile of Tonsillar Squamous Cell Carcinomas Using Targeted Next-Generation Sequencing
    Park, Ha Young
    Lee, Joong Seob
    Wee, Jee Hye
    Kang, Jeong Wook
    Kim, Eun Soo
    Koo, Taeryool
    Hwang, Hee Sung
    Kim, Hyo Jung
    Kang, Ho Suk
    Lim, Hyun
    Kim, Nan Young
    Nam, Eun Sook
    Cho, Seong Jin
    Kwon, Mi Jung
    BIOMEDICINES, 2023, 11 (03)
  • [36] Genome-Wide Copy Number Variation and Targeted Next-Generation Sequencing Studies of Merkel Cell Carcinoma
    Carter, M.
    Gaston, D.
    Huang, W.
    Greer, W.
    Pasternak, S.
    Ly, T.
    Walsh, N. M.
    JOURNAL OF MOLECULAR DIAGNOSTICS, 2017, 19 (06): : 1012 - 1013
  • [37] Clinical correlation and diagnostic value of circular RNA determined via next-generation sequencing in lung squamous cell carcinomas
    Xu, Fei
    Liu, Yang
    Dai, Yu
    Li, Chun-Sheng
    Li, Chun-Sun
    Chang, Yan
    Ma, Yong-Fu
    Li, Yun-Jing
    Chen, Liang-An
    INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, 2018, 11 (11): : 11706 - +
  • [38] MULTIPLE NEUROENDOCRINE CARCINOMAS (SO-CALLED MERKEL CELL TUMORS) OF THE SKIN - REPORT ON 2 CASES WITH UNIQUE CLINICAL COURSE
    KATENKAMP, D
    WATZIG, V
    VIRCHOWS ARCHIV A-PATHOLOGICAL ANATOMY AND HISTOPATHOLOGY, 1984, 404 (04) : 403 - 411
  • [39] Next-generation sequencing informs diagnosis and identifies unexpected therapeutic targets in lung squamous cell carcinomas
    Sands, Jacob M.
    Nguyen, Tom
    Shivdasani, Priyanka
    Sacher, Adrian G.
    Cheng, Michael L.
    Alden, Ryan S.
    Janne, Pasi A.
    Kuo, Frank C.
    Oxnard, Geoffrey R.
    Sholl, Lynette M.
    LUNG CANCER, 2020, 140 : 35 - 41
  • [40] Association of Merkel Cell Polyomavirus Status With p53, RB1, and PD-L1 Expression and Patient Prognosis in Merkel Cell Carcinomas: Clinical, Morphologic, and Immunohistochemical Evaluation of 17 Cases
    Ogut, Betul
    Bayram, Elif Kolay
    Inan, Mehmet Arda
    Kestel, Selin
    Erdem, Ozlem
    APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY, 2023, 31 (06) : 371 - 378