Merkel cell polyomavirus and human papilloma virus in proliferative skin lesions arising in patients treated with BRAF inhibitors.
The potential role of oncogenic viruses mediating development of proliferative skin lesions in patients treated with RAF inhibitors is poorly understood. The objective of this study was to investigate human papilloma virus (HPV) and Merkel cell polyomavirus (MCPyV) in skin lesions among patients treated with RAF inhibitors with the help of a case series describing prevalence of HPV, MCPyV, and RAS mutations in skin biopsies obtained from patients receiving RAF inhibitors and developing cutaneous lesions. HPV-DNA was amplified by PCR utilizing multiple nested primer systems designed for detection of a broad range of HPV types. MCPyV copy number determination with real time PCR technology was performed by a "Quantification of MCPyV, small t region" kit. Thirty-six patients were tested (squamous cell carcinoma (SCC) = 14; verruca vulgaris = 15; other = 11). Nine of 12 SCCs (75 %) and eight of 13 verruca vulgaris lesions (62 %) tested positive for MCPyV whereas none of the normal skin biopsies obtained from nine of these patients tested positive for MCPyV (p = 0.0007). HPV incidence in cutaneous SCCs was not different compared to normal skin (50 vs. 56 %, p = 0.86). The association between MCPyV and proliferative skin lesions after RAF inhibitor therapy merits further investigation.
Sarah Cannon Research Institute, 1800 Williams Street, Suite 300, Denver, CO, 80218, USA. gerald.falchook@scresearch.net.
G S
GS
Falchook
Department of Dermatology, The University of Texas Health Science Center at Houston, Houston, TX, USA.
P
P
Rady
Baylor College of Medicine, Houston, TX, USA.
J C
JC
Konopinski
Division of Internal Medicine, Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
N
N
Busaidy
Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
K
K
Hess
Division of Internal Medicine, Department of Dermatology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
S
S
Hymes
Baylor College of Medicine, Houston, TX, USA.
H P
HP
Nguyen
Division of Pathology and Laboratory Medicine, Departments of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
V G
VG
Prieto
Florida Cancer Specialists, Orlando, FL, USA.
E
E
Bustinza-Linares
Division of Cancer Medicine, Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Q
Q
Lin
Division of Cancer Medicine, Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
K L
KL
Parkhurst
Division of Cancer Medicine, Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
D S
DS
Hong
Division of Internal Medicine, Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
S
S
Sherman
Department of Dermatology, The University of Texas Health Science Center at Houston, Houston, TX, USA.
S K
SK
Tyring
Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
R
R
Kurzrock
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000473:pathology / Q000821:virology*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics; D059965:Merkel cell polyomavirus / Q000302:isolation & purification*; D008875:Middle Aged; D009154:Mutation; D010091:Oximes / Q000009:adverse effects* / Q000627:therapeutic use; D027383:Papillomaviridae / Q000302:isolation & purification*; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D012189:Retrospective Studies; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000821:virology*; D014860:Warts / Q000139:chemically induced / Q000473:pathology / Q000821:virology*
D007093:Imidazoles; D010091:Oximes; D047428:Protein Kinase Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib
BRAF; Dabrafenib; HPV; Merkel cell polyomavirus; Squamous cell carcinoma; Verruca vulgaris