Genomic portfolio of Merkel cell carcinoma as determined by comprehensive genomic profiling: implications for targeted therapeutics. Oncotarget 2016 Apr 26;7(17):23454-67
Date
03/17/2016Pubmed ID
26981779Pubmed Central ID
PMC5029639DOI
10.18632/oncotarget.8032Scopus ID
2-s2.0-84966681514 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
Merkel cell carcinoma is an ultra-rare cutaneous neuroendocrine cancer for which approved treatment options are lacking. To better understand potential actionability, the genomic landscape of Merkel cell cancers was assessed. The molecular aberrations in 17 patients with Merkel cell carcinoma were, on physician request, tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory (Foundation Medicine, Cambridge, MA) using next-generation sequencing (182 or 236 genes) and analyzed by N-of-One, Inc. (Lexington, MA). There were 30 genes harboring aberrations and 60 distinct molecular alterations identified in this patient population. The most common abnormalities involved the TP53 gene (12/17 [71% of patients]) and the cell cycle pathway (CDKN2A/B, CDKN2C or RB1) (12/17 [71%]). Abnormalities also were observed in the PI3K/AKT/mTOR pathway (AKT2, FBXW7, NF1, PIK3CA, PIK3R1, PTEN or RICTOR) (9/17 [53%]) and DNA repair genes (ATM, BAP1, BRCA1/2, CHEK2, FANCA or MLH1) (5/17 [29%]). Possible cognate targeted therapies, including FDA-approved drugs, could be identified in most of the patients (16/17 [94%]). In summary, Merkel cell carcinomas were characterized by multiple distinct aberrations that were unique in the majority of analyzed cases. Most patients had theoretically actionable alterations. These results provide a framework for investigating tailored combinations of matched therapies in Merkel cell carcinoma patients.
Author List
Cohen PR, Tomson BN, Elkin SK, Marchlik E, Carter JL, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Biomarkers, TumorCarcinoma, Merkel Cell
Genomics
High-Throughput Nucleotide Sequencing
Humans
Molecular Targeted Therapy
Precision Medicine
Skin Neoplasms