Dynamic and unpredictable changes in mutant allele fractions of BRAF and NRAS during visceral progression of cutaneous malignant melanoma

BMC Cancer
V DomaJ Tímár

Abstract

Data indicate that primary cutaneous melanomas are characterized by clonal heterogeneity associated with oncogenic drivers. Less data are available on the clonal changes occurring during melanoma progression. We therefore wished to analyse these changes in skin melanomas in common sites of visceral metastases as compared to the primary tumor. An autopsy cohort of 50 patients with BRAF- and NRAS-mutant cutaneous metastatic melanomas including 139 visceral metastases was analysed for mutant allele fractions (MAF), determined by pyrosequencing and corrected for tumor/normal ratio. MAF levels were also classified as high (> 40%), medium (15-40%) or low (< 15%). Contrary to NRAS mutant cases, in BRAF-mutant melanomas MAFs were found to be significantly increased in visceral metastases compared to the primary due to the significantly higher levels in lung-, adrenal gland-, intestinal- and kidney metastases. The incidence of the three MAF variants in BRAF-mutant primaries was similar, whereas the high MAF cases were found to be increased in metastases. On the other hand, medium MAF levels were more common in case of NRAS-mutant tumors. Only 31.3% of BRAF mutant- and 50% of NRAS mutant cases maintained the MAF profile of the primary in...Continue Reading

References

May 23, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Maria ColombinoGiuseppe Palmieri
Nov 8, 2013·British Journal of Cancer·L HeinzerlingR Schneider-Stock
Mar 4, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alexander M Menzies, Georgina V Long
Jun 17, 2014·Melanoma Research·Celeste LebbéSamia Mourah
Nov 8, 2014·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Joshua R BradishLiang Cheng
Nov 14, 2014·PloS One·Li DingJeffrey S Weber
Jul 5, 2015·BMC Cancer·Zofia Hélias-RodzewiczJean-François Emile
Aug 8, 2015·Nature Medicine·Ash A AlizadehJessica Zucman-Rossi
Aug 20, 2015·Proceedings of the National Academy of Sciences of the United States of America·J Zachary SanbornRaymond J Cho
Nov 17, 2015·The Journal of Investigative Dermatology·Gregory A Chang, David Polsky
Apr 29, 2016·Science·Samra Turajlic, Charles Swanton
Nov 20, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Geoff MacintyreChristopher M Hovens
Dec 22, 2016·Pigment Cell & Melanoma Research·Nima Mesbah ArdakaniBenhur Amanuel
Jul 3, 2017·BMC Dermatology·Zofia Hélias-RodzewiczJean-François Emile
Aug 9, 2017·British Journal of Cancer·Nikki R AdlerVictoria J Mar
Nov 18, 2017·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Liang ChengRodolfo Montironi

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Methods Mentioned

BETA
PCR

Software Mentioned

SPSS
PyroMark
Array Designer
PyroMarkQ24
Chromas Lite

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