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
  • [41] Exploring the miRNA-mRNA Regulatory Network in Clear Cell Renal Cell Carcinomas by Next-Generation Sequencing Expression Profiles
    Mueller, Soeren
    Nowak, Katharina
    BIOMED RESEARCH INTERNATIONAL, 2014, 2014
  • [42] Clinical Outcomes of Patients with Pulmonary Large Cell Neuroendocrine Carcinoma Characterized by Next-Generation Sequencing
    Sabari, Joshua
    Rudin, Charles
    Rekhtman, Natasha
    JOURNAL OF THORACIC ONCOLOGY, 2016, 11 (11) : S283 - S283
  • [43] Comprehensive T-cell immunophenotyping and next-generation sequencing of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinomas
    Poropatich, Kate
    Fontanarosa, Joel
    Swaminathan, Suchitra
    Dittmann, Dave
    Chen, Siqi
    Samant, Sandeep
    Zhang, Bin
    JOURNAL OF PATHOLOGY, 2017, 243 (03): : 354 - 365
  • [44] Next-Generation Sequencing of a Cohort of Pulmonary Large Cell Carcinomas Reclassified by World Health Organization 2015 Criteria
    Driver, Brandon R.
    Portier, Bryce P.
    Mody, Dina R.
    Deavers, Michael
    Bernicker, Eric H.
    Kim, Min P.
    Teh, Bin S.
    Santacruz, Jose F.
    Kopas, Lisa
    Munden, Reginald F.
    Cagle, Philip T.
    ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE, 2016, 140 (04) : 312 - 317
  • [45] Next-generation sequencing identifies Notch receptors as integral tumor suppressors in cutaneous and lung squamous cell carcinomas
    Wang, N. J.
    Sanborn, Z.
    Arnett, K. L.
    Bayston, L. J.
    Liao, W.
    Proby, C. M.
    Leigh, I. M.
    Gordon, P. B.
    Sharma, M.
    North, J. P.
    Vemula, S. S.
    Mauro, T. M.
    Neuhaus, I. M.
    LeBoit, P. E.
    Kwok, P.
    Arron, S. T.
    Bale, A. E.
    Haussler, D.
    Cleaver, J. E.
    Gray, J. W.
    Spellman, P. T.
    South, A. P.
    Aster, J. C.
    Blacklow, S. C.
    Cho, R. J.
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2012, 132 : S23 - S23
  • [46] Comprehensive analysis of driver mutations in Chinese squamous cell lung carcinomas by targeted next-generation sequencing.
    Yang, Sheng
    Tao, Dan
    Wu, Di
    Zhang, Ningning
    Wang, Lin
    Liu, Yutao
    Han, Xiaohong
    Shi, Yuankai
    JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (15)
  • [47] Divergent Molecular Pathogenesis of EBV-Negative Lymphoepithelial Carcinomas Arising in the Nasopharynx and Urinary Bladder Revealed by Next-Generation Sequencing
    Buelow, Benjamin
    Naccache, Samia
    Yu, Guixia
    Joseph, Nancy
    Chiu, Charles
    LABORATORY INVESTIGATION, 2016, 96 : 219A - 219A
  • [48] Comparative analysis of B cell-related marker and immunoglobulin expressions between MCPyV-positive and MCPyV-negative Merkel cell carcinomas
    Hayashi, K.
    Nonaka, D.
    Matsushita, M.
    Takata, K.
    Iwasaki, T.
    Kuwamoto, S.
    Kato, M.
    Nagata, K.
    Kitamura, Y.
    Yoshino, T.
    Murakami, I.
    VIRCHOWS ARCHIV, 2014, 465 : S182 - S182
  • [49] Divergent Molecular Pathogenesis of EBV-Negative Lymphoepithelial Carcinomas Arising in the Nasopharynx and Urinary Bladder Revealed by Next-Generation Sequencing
    Buelow, Benjamin
    Naccache, Samia
    Yu, Guixia
    Joseph, Nancy
    Chiu, Charles
    MODERN PATHOLOGY, 2016, 29 : 219A - 219A
  • [50] Next-generation sequencing in the molecular classification of endometrial carcinomas: Experience with 270 cases suggesting a potentially more aggressive clinical behavior of multiple classifier endometrial carcinomas
    Michalova, Kvetoslava
    Strakova-Peterikova, Andrea
    Ondic, Ondrej
    Vanecek, Tomas
    Michal, Michael
    Hejhalova, Nikola
    Holub, Petr
    Slavik, Petr
    Hluchy, Adam
    Gettse, Polina
    Daum, Ondrej
    Svajdler, Marian
    Michal, Michal
    Presl, Jiri
    VIRCHOWS ARCHIV, 2024,