PMID- 26141748 OWN - NLM STAT- MEDLINE DCOM- 20160414 LR - 20181113 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 15 DP - 2015 Jul 4 TI - Variations of BRAF mutant allele percentage in melanomas. PG - 497 LID - 10.1186/s12885-015-1515-3 [doi] LID - 497 AB - BACKGROUND: BRAF mutations are present in 40% of human skin melanomas. Mutated tumors with an increased percentage of BRAF mutant alleles (BRAF-M%) may have a better response to RAF/MEK inhibitors. We evaluated the BRAF-M% in melanomas, and the genetic causes of its variation. METHODS: BRAF-M% was quantified by pyrosequencing, real-time PCR (rtPCR) and/or picoliter-droplet PCR (dPCR). BRAF mutant expression was detected by immunohistochemistry. Chromosomal alterations were analyzed with fluorescence in situ hybridization (FISH), and single nucleotide polymorphism (SNP) arrays. RESULTS: BRAF-M% quantification obtained with pyrosequencing was highly correlated (R = 0.94) with rtPCR, and with dPCR. BRAF-M% quantified from DNA and RNA were also highly correlated (R = 0.98). Among 368 samples with >80% tumor cells, 38.6% had a BRAF (V600E) mutation. Only 66.2% cases were heterozygous (BRAF-M% 30 to 60%). Increased BRAF-M% (>60%) was observed in 19% of cases. FISH showed a polysomy of chromosome 7 in 13.6%, 35.3% and 54.5% of BRAF wild-type, heterozygous and non-heterozygous BRAF-mutated samples, respectively (P < 0.005). Amplification (5.6%) and loss (3.2%) of BRAF locus were rare. By contrast, chromosome 7 was disomic in 27/27 BRAF-mutated nevi. CONCLUSIONS: BRAF-M% is heterogeneous and frequently increased in BRAF-mutant melanomas. Aneuploidy of chromosome 7 is more frequent in BRAF mutant melanomas, specifically in those with high BRAF-M%. FAU - Helias-Rodzewicz, Zofia AU - Helias-Rodzewicz Z AD - EA4340, Versailles University, Boulogne-Billancourt, France. zofia.helias@aphp.fr. AD - Department of Pathology, Ambroise Pare Hospital, APHP, Boulogne-Billancourt, France. zofia.helias@aphp.fr. FAU - Funck-Brentano, Elisa AU - Funck-Brentano E AD - EA4340, Versailles University, Boulogne-Billancourt, France. elisa.funck-brentano@aphp.fr. AD - Department of Dermatology, Ambroise Pare Hospital, APHP, Boulogne-Billancourt, France. elisa.funck-brentano@aphp.fr. FAU - Baudoux, Laure AU - Baudoux L AD - EA4340, Versailles University, Boulogne-Billancourt, France. laure.baudoux@yahoo.fr. FAU - Jung, Chan Kwon AU - Jung CK AD - Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea. ckjung@catholic.ac.kr. FAU - Zimmermann, Ute AU - Zimmermann U AD - EA4340, Versailles University, Boulogne-Billancourt, France. us.zimmermann@gmail.fr. AD - Department of Pathology, Ambroise Pare Hospital, APHP, Boulogne-Billancourt, France. us.zimmermann@gmail.fr. FAU - Marin, Cristi AU - Marin C AD - EA4340, Versailles University, Boulogne-Billancourt, France. cristi.marin@aphp.fr. AD - Department of Pathology, Ambroise Pare Hospital, APHP, Boulogne-Billancourt, France. cristi.marin@aphp.fr. FAU - Clerici, Thierry AU - Clerici T AD - EA4340, Versailles University, Boulogne-Billancourt, France. thierryclerici@noos.fr. AD - Department of Pathology, Ambroise Pare Hospital, APHP, Boulogne-Billancourt, France. thierryclerici@noos.fr. FAU - Le Gall, Catherine AU - Le Gall C AD - EA4340, Versailles University, Boulogne-Billancourt, France. legall.catherine@voila.fr. AD - Department of Pathology, Ambroise Pare Hospital, APHP, Boulogne-Billancourt, France. legall.catherine@voila.fr. FAU - Peschaud, Frederique AU - Peschaud F AD - EA4340, Versailles University, Boulogne-Billancourt, France. frederique.peschaud@aphp.fr. AD - Department of Surgery, Ambroise Pare Hospital, APHP, Boulogne-Billancourt, France. frederique.peschaud@aphp.fr. FAU - Taly, Valerie AU - Taly V AD - INSERM UMR-S1147, University Paris Sorbonne Cite, Paris, France. valerie.taly@parisdescartes.fr. FAU - Saiag, Philippe AU - Saiag P AD - EA4340, Versailles University, Boulogne-Billancourt, France. philippe.saiag@uvsq.fr. AD - Department of Dermatology, Ambroise Pare Hospital, APHP, Boulogne-Billancourt, France. philippe.saiag@uvsq.fr. FAU - Emile, Jean-Francois AU - Emile JF AD - EA4340, Versailles University, Boulogne-Billancourt, France. jean-francois.emile@uvsq.fr. AD - Department of Pathology, Ambroise Pare Hospital, APHP, Boulogne-Billancourt, France. jean-francois.emile@uvsq.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150704 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - EC 2.7.11.1 (BRAF protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf) SB - IM MH - Aneuploidy MH - Chromosomes, Human, Pair 7/genetics MH - Heterozygote MH - Humans MH - In Situ Hybridization, Fluorescence MH - Melanoma/epidemiology/*genetics MH - Polymorphism, Single Nucleotide/genetics MH - Proto-Oncogene Proteins B-raf/*genetics MH - Real-Time Polymerase Chain Reaction PMC - PMC4491198 EDAT- 2015/07/05 06:00 MHDA- 2016/04/15 06:00 PMCR- 2015/07/04 CRDT- 2015/07/05 06:00 PHST- 2015/01/09 00:00 [received] PHST- 2015/06/26 00:00 [accepted] PHST- 2015/07/05 06:00 [entrez] PHST- 2015/07/05 06:00 [pubmed] PHST- 2016/04/15 06:00 [medline] PHST- 2015/07/04 00:00 [pmc-release] AID - 10.1186/s12885-015-1515-3 [pii] AID - 1515 [pii] AID - 10.1186/s12885-015-1515-3 [doi] PST - epublish SO - BMC Cancer. 2015 Jul 4;15:497. doi: 10.1186/s12885-015-1515-3.