%0 Journal Article %T Tumor mutational burden and response to PD-1 inhibitors in a case series of patients with metastatic desmoplastic melanoma %+ Institut de Génétique et Développement de Rennes (IGDR) %+ Foundation Medicine Inc %+ City of Hope Comprehensive Cancer Center [Duarte] %+ Hadassah Hebrew University Medical Center [Jerusalem] %+ Georgetown Lombardi Comprehensive Cancer Center %+ H. Lee Moffitt Cancer Center and Research Institute %+ University of California [Los Angeles] (UCLA) %A Boussemart, Lise %A Johnson, Adrienne %A Schrock, Alexa B %A Pal, Sumanta K %A Frampton, Garrett M %A Fabrizio, David %A Chalmers, Zachary %A Lotem, Michal %A Gibney, Geoffrey %A Russell, Jeffery %A Chmielowski, Bartosz %A Ross, Jeffrey S %A Stephens, Philip J %A Miller, Vincent A %A Ali, Siraj M %< avec comité de lecture %@ 0190-9622 %J Journal of The American Academy of Dermatology %I Elsevier %V 80 %N 6 %P 1780-1782 %8 2019-06 %D 2019 %R 10.1016/j.jaad.2018.12.020 %M 30576761 %K pembrolizumab %K hypermutated %K PD-1 %K UV signature %K Desmoplastic melanoma %Z Life Sciences [q-bio]/Human health and pathology/Dermatology %Z Life Sciences [q-bio]/Cancer %Z Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]Journal articles %X Desmoplastic melanoma (DM) represents an infrequently occurring and distinct histologic pattern of melanomas, often lacking mutations in genes typically altered in conventional melanomas including BRAF, NRAS, and KIT. We aimed at better characterizing the genetic profile of this subgroup of melanomas to match patients with available therapies. Pathology reports were reviewed for 1,240 consecutive melanoma cases sequenced by comprehensive genomic profiling (CGP) using a hybrid-capture based next generation sequencing during the course of clinical care. The mutational profile of the 12 DM identified was compared with the remaining 1,228 melanomas examined. We report a median tumor mutational burden (TMB) of 77 mutations per megabase (mut/Mb) in DM, which was significantly greater than a median of 35 mut/Mb in non-DM. A UV DNA damage signature was detected in 10/12 (83%) DM. For a subset of patients with available clinical course, we report that 100% (5/5) had clinical benefit from treatment with PD-1 inhibitors as monotherapy. TMB and UV signature show significant promise as an approach to identify patients who are likely to benefit from PD-1 targeted immunotherapy. %G English %2 https://univ-rennes.hal.science/hal-02020674/document %2 https://univ-rennes.hal.science/hal-02020674/file/Tumor%20mutational%20burden%20and%20response%20to%20PD-1%20inhibitors.pdf %L hal-02020674 %U https://univ-rennes.hal.science/hal-02020674 %~ UNIV-RENNES1 %~ CNRS %~ IFR140 %~ IGDR %~ STATS-UR1 %~ IGDR-EGO %~ UR1-UFR-SVE %~ UR1-HAL %~ UR1-SDV %~ TEST-UR-CSS %~ UNIV-RENNES %~ TEST-HALCNRS %~ UR1-BIO-SA