PMID- 25876211
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150618
LR  - 20200929
IS  - 2193-8210 (Print)
IS  - 2190-9172 (Electronic)
VI  - 5
IP  - 2
DP  - 2015 Jun
TI  - Merkel Cell Carcinoma with a Suppressor of Fused (SUFU) Mutation: Case Report and 
      Potential Therapeutic Implications.
PG  - 129-43
LID - 10.1007/s13555-015-0074-5 [doi]
AB  - INTRODUCTION: Merkel cell carcinoma is a neuroendocrine malignancy. Suppressor of 
      fused (SUFU) is a tumor suppressor oncogene that participates in the Hedgehog 
      (Hh) signaling pathway. The aim of the study was to describe a patient whose 
      Merkel cell carcinoma demonstrated a SUFU genomic alteration. CASE STUDY: The Hh 
      signaling pathway is involved in the pathogenesis of several tumors, including 
      nevoid basal cell carcinoma syndrome that is associated with an alteration of the 
      patched-1 (PTCH1) gene. Targeted molecular therapy against smoothened (SMO) with 
      vismodegib has been shown to be an effective therapeutic intervention for 
      patients with PTCH-1 mutation. The reported patient was presented with metastatic 
      Merkel cell carcinoma. Analysis of his tumor, using a next-generation 
      sequencing-based assay, demonstrated a genomic aberration of SUFU protein, a 
      component of the Hh signaling pathway that acts downstream to SMO and, therefore, 
      is unlikely to be responsive to vismodegib. Of interest, arsenic trioxide or 
      bromo and extra C-terminal inhibitors impact signals downstream to SUFU, making 
      this aberration conceivably druggable. His tumor has initially been managed with 
      chemotherapy (carboplatin and etoposide) and subsequent radiation therapy is 
      planned. CONCLUSION: The pathogenesis of Merkel cell carcinoma is multifactorial, 
      and related to ultraviolet radiation exposure, immunosuppression, and Merkel cell 
      polyomavirus. We report a patient with a mutation in SUFU, a potentially 
      actionable component of the Hh signaling pathway.
FAU - Cohen, Philip R
AU  - Cohen PR
AD  - Department of Dermatology, University of California San Diego, San Diego, CA, 
      USA, mitehead@gmail.com.
FAU - Kurzrock, Razelle
AU  - Kurzrock R
LA  - eng
PT  - Journal Article
DEP - 20150415
PL  - Switzerland
TA  - Dermatol Ther (Heidelb)
JT  - Dermatology and therapy
JID - 101590450
PMC - PMC4470960
EDAT- 2015/04/16 06:00
MHDA- 2015/04/16 06:01
PMCR- 2015/04/15
CRDT- 2015/04/16 06:00
PHST- 2015/02/27 00:00 [received]
PHST- 2015/04/16 06:00 [entrez]
PHST- 2015/04/16 06:00 [pubmed]
PHST- 2015/04/16 06:01 [medline]
PHST- 2015/04/15 00:00 [pmc-release]
AID - 74 [pii]
AID - 10.1007/s13555-015-0074-5 [doi]
PST - ppublish
SO  - Dermatol Ther (Heidelb). 2015 Jun;5(2):129-43. doi: 10.1007/s13555-015-0074-5. 
      Epub 2015 Apr 15.