Merkel Cell Carcinoma

Ramahi, Emma; Choi, J. Isabelle; Fuller, Clifton D.; Eng, Tony Y.

doi:10.1097/coc.0b013e318210f83c

Cited by 50 publications

(54 citation statements)

References 107 publications

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“…MCC has propensity for early spread and recurrence and while surgery and radiotherapy can achieve high rates of locoregional control, chemotherapy rarely provides durable responses for distant metastatic disease (4). The deployment of improved targeted therapies is likely to be achieved through a better understanding of MCC biology.…”

Section: Introductionmentioning

confidence: 99%

UV-Associated Mutations Underlie the Etiology of MCV-Negative Merkel Cell Carcinomas

et al. 2015

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Merkel cell carcinoma (MCC) is an uncommon, but highly malignant, cutaneous tumor. Merkel cell polyoma virus (MCV) has been implicated in a majority of MCC tumors; however, viralnegative tumors have been reported to be more prevalent in some geographic regions subject to high sun exposure. While the impact of MCV and viral T-antigens on MCC development has been extensively investigated, little is known about the etiology of viralnegative tumors. We performed targeted capture and massively parallel DNA sequencing of 619 cancer genes to compare the gene mutations and copy number alterations in MCV-positive (n ¼ 13) and -negative (n ¼ 21) MCC tumors and cell lines. We found that MCV-positive tumors displayed very low mutation rates, but MCV-negative tumors exhibited a high mutation burden associated with a UV-induced DNA damage signature. All viral-negative tumors harbored mutations in RB1, TP53, and a high frequency of mutations in NOTCH1 and FAT1. Additional mutated or amplified cancer genes of potential clinical importance included PI3K (PIK3CA, AKT1, PIK3CG) and MAPK (HRAS, NF1) pathway members and the receptor tyrosine kinase FGFR2. Furthermore, looking ahead to potential therapeutic strategies encompassing immune checkpoint inhibitors such as anti-PD-L1, we also assessed the status of T-cell-infiltrating lymphocytes (TIL) and PD-L1 in MCC tumors. A subset of viral-negative tumors exhibited high TILs and PD-L1 expression, corresponding with the higher mutation load within these cancers. Taken together, this study provides new insights into the underlying biology of viral-negative MCC and paves the road for further investigation into new treatment opportunities. Cancer Res; 75(24); 5228-34. Ó2015 AACR.

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Section: Introductionmentioning

confidence: 99%

UV-Associated Mutations Underlie the Etiology of MCV-Negative Merkel Cell Carcinomas

et al. 2015

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“…Currently, adjuvant RT is advocated because MCC has a high incidence of nodal and metastatic disease. 27,28 A previously unaddressed question was whether RT was beneficial in those patients specifically known to be node negative. Our study found that there was no statistical survival advantage to giving adjuvant RT to patients with a negative SLNB.…”

Section: Commentsmentioning

confidence: 99%