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Table 2 NGS-based molecular alterations in BRAF -positive melanoma responders

From: Next generation sequencing of exceptional responders with BRAF-mutant melanoma: implications for sensitivity and resistance

Case no. BRAFmutation Type of targeted drug Treatment start date Best response (%) TTF (months)a Sampling date; time from treatmentb Molecular analysis by NGS
Mutations Amplifications/deletions Truncations
1 V600E BRAF inhibitor 9/17/2009 CR (−100) 28.7+ 5/1/2009; −4 months BRAF (V600E) None None
2 V600E BRAF inhibitor 10/7/2009 CR (−100) 27.4+ 1/22/2009; −9 months BRAF (V600E); BRAF (T599S) AURKA amplification; BRAF amplification None
T599S
3 V600E BRAF inhibitor 1/27/2010 CR (−100) 23.6+ 8/19/2005; −53 months Nonec None None
4 V600E BRAF + MEK inhibitor 11/11/2010 PR (−34) 11.2 5/17/2011; +6 months APC (R1171H); BRAF (V600E); NRAS (Q61R) PTEN deletion RB1 truncation
5 V600E BRAF inhibitor 6/17/2009 PR (−38) 7.9 12/2/2009; +6 months BRAF (V600E) CDKN2A deletion; CDKN2B deletion; PAX5 deletion None
       3/23/2010; +9 months BRAF (V600E) CDKN2A deletion; CDKN2B deletion; PAX5 deletion NF1 truncation
       8/24/2011; +26 months None None None
6 V600E MEK inhibitor 4/1/2010 PR (−53) 7.0 9/17/2007; −31 months BRAF (V600E) None None
7 V600E BRAF inhibitor 1/12/2010 PR (−48) 5.7 11/5/2009; −2 months BRAF (V600E) MITF amplification None
8 V600E BRAF + MEK inhibitor 9/3/2010 CR (−100) 5.6 4/7/2009; −17 months BRAF (V600E); NF1 (R 440*)d None None
9 V600E BRAF inhibitor 1/27/2010 PR (−75) 4.2 11/11/2009; −2 months BRAF (V600E) BRAF amplification; MET amplification; CDKN2A deletion; CDKN2B deletion ATM truncation
10 V600E BRAF inhibitor 4/15/2010 PR (−54) 3.0 12/11/2009; −4 months BRAF (V600E) MYC amplification; CDKN2A deletion None
  1. a ‘+’ = continuing on the study when data was censored.
  2. b ‘ + ’ = number of months biopsy was taken after treatment; '-' = number of months biopsy preceded treatment.
  3. c = tissue sample obtained on 10/29/2008 was BRAF mutation-positive (V600E) by single PCR assay (case #3).
  4. d = tissue sample obtained from a progressive hepatic lesion on 12/27/2010 had an NRAS mutation (Q61K) in codon 61 by single PCR assay (case #8).
  5. Abbreviations:CR Complete response, NGS Next generation sequencing, PR Partial response, TTF Time to treatment failure.