Skip to main content
Top
Published in: Virchows Archiv 3/2018

01-09-2018 | Brief Report

Comparison of targeted next generation sequencing (NGS) versus isolated BRAF V600E analysis in patients with metastatic melanoma

Authors: Meng-Lei Zhu, Lan Zhou, Navid Sadri

Published in: Virchows Archiv | Issue 3/2018

Login to get access

Abstract

Molecular testing on advanced metastatic melanoma is critical for guiding targeted therapy. Traditionally, this analysis has relied on isolated BRAF V600E analysis; however, more recently targeted next generation sequencing (NGS) is being utilized. The clinical utility of BRAF V600E allele-specific PCR and targeted NGS were compared for metastatic melanoma samples sent to UHCMC pathology during a two and half year span. In two thirds of cases, negative for BRAF V600E, additional mutations were detected that may stratify patients for potential or approved targeted therapies. Targeted-NGS testing is feasible and cost-affordable and provides additional potentially actionable information for patients with BRAF V600E/K negative metastatic melanoma. Based on this analysis, we have adopted to screen patients with advanced melanoma with allele-specific V600E/K PCR and reflex negative cases for targeted NGS to maximize patient benefit.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ascierto PA, Minor D, Ribas A, Lebbe C, O'Hagan A, Arya N, Guckert M, Schadendorf D, Kefford RF, Grob JJ, Hamid O, Amaravadi R, Simeone E, Wilhelm T, Kim KB, Long GV, Martin AM, Mazumdar J, Goodman VL, Trefzer U (2013) Phase II trial (BREAK-2) of the BRAF inhibitor DaBRAFenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol 31:3205–3211. https://doi.org/10.1200/JCO.2013.49.8691 CrossRefPubMed Ascierto PA, Minor D, Ribas A, Lebbe C, O'Hagan A, Arya N, Guckert M, Schadendorf D, Kefford RF, Grob JJ, Hamid O, Amaravadi R, Simeone E, Wilhelm T, Kim KB, Long GV, Martin AM, Mazumdar J, Goodman VL, Trefzer U (2013) Phase II trial (BREAK-2) of the BRAF inhibitor DaBRAFenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol 31:3205–3211. https://​doi.​org/​10.​1200/​JCO.​2013.​49.​8691 CrossRefPubMed
2.
go back to reference Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, McArthur GA, Hutson TE, Moschos SJ, Flaherty KT, Hersey P, Kefford R, Lawrence D, Puzanov I, Lewis KD, Amaravadi RK, Chmielowski B, Lawrence HJ, Shyr Y, Ye F, Li J, Nolop KB, Lee RJ, Joe AK, Ribas A (2012) Survival in BRAF V600–mutant advanced melanoma treated with vemurafenib. N Engl J Med 366:707–714. https://doi.org/10.1056/NEJMoa1112302 CrossRefPubMedPubMedCentral Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, McArthur GA, Hutson TE, Moschos SJ, Flaherty KT, Hersey P, Kefford R, Lawrence D, Puzanov I, Lewis KD, Amaravadi RK, Chmielowski B, Lawrence HJ, Shyr Y, Ye F, Li J, Nolop KB, Lee RJ, Joe AK, Ribas A (2012) Survival in BRAF V600–mutant advanced melanoma treated with vemurafenib. N Engl J Med 366:707–714. https://​doi.​org/​10.​1056/​NEJMoa1112302 CrossRefPubMedPubMedCentral
3.
go back to reference Akbani R, Akdemir KC, Aksoy BA, Albert M, Ally A, Amin SB, Arachchi H, Arora A, Auman JT, Ayala B, Baboud J, Balasundaram M, Balu S, Barnabas N, Bartlett J, Bartlett P, Bastian BC, Baylin SB, Behera M, Belyaev D, Benz C, Bernard B, Beroukhim R, Bir N, Black AD, Bodenheimer T, Boice L, Boland GM, Bono R, Bootwalla MS, Bosenberg M, Bowen J, Bowlby R, Bristow CA, Brockway-Lunardi L, Brooks D, Brzezinski J, Bshara W, Buda E, Burns WR, Butterfield YSN, Button M, Calderone T, Cappellini GA, Carter C, Carter SL, Cherney L, Cherniack AD, Chevalier A, Chin L, Cho J, Cho RJ, Choi YL, Chu A, Chudamani S, Cibulskis K, Ciriello G, Clarke A, Coons S, Cope L, Crain D, Curley E, Danilova L, D’Atri S, Davidsen T, Davies MA, Delman KA, Demchok JA, Deng QA, Deribe YL, Dhalla N, Dhir R, DiCara D, Dinikin M, Dubina M, Ebrom JS, Egea S, Eley G, Engel J, Eschbacher JM, Fedosenko KV, Felau I, Fennell T, Ferguson ML, Fisher S, Flaherty KT, Frazer S, Frick J, Fulidou V, Gabriel SB, Gao J, Gardner J, Garraway LA, Gastier-Foster JM, Gaudioso C, Gehlenborg N, Genovese G, Gerken M, Gershenwald JE, Getz G, Gomez-Fernandez C, Gribbin T, Grimsby J, Gross B, Guin R, Gutschner T, Hadjipanayis A, Halaban R, Hanf B, Haussler D, Haydu LE, Hayes DN, Hayward NK, Heiman DI, Herbert L, Herman JG, Hersey P, Hoadley KA, Hodis E, Holt RA, Hoon DSB, Hoppough S, Hoyle AP, Huang FW, Huang M, Huang S, Hutter CM, Ibbs M, Iype L, Jacobsen A, Jakrot V, Janning A, Jeck WR, Jefferys SR, Jensen MA, Jones CD, Jones SJM, Ju Z, Kakavand H, Kang H, Kefford RF, Khuri FR, Kim J, Kirkwood JM, Klode J, Korkut A, Korski K, Krauthammer M, Kucherlapati R, Kwong LN, Kycler W, Ladanyi M, Lai PH, Laird PW, Lander E, Lawrence MS, Lazar AJ, Łaźniak R, Lee D, Lee JE, Lee J, Lee K, Lee S, Lee W, Leporowska E, Leraas KM, Li HI, Lichtenberg TM, Lichtenstein L, Lin P, Ling S, Liu J, Liu O, Liu W, Long GV, Lu Y, Ma S, Ma Y, Mackiewicz A, Mahadeshwar HS, Malke J, Mallery D, Manikhas GM, Mann GJ, Marra MA, Matejka B, Mayo M, Mehrabi S, Meng S, Meyerson M, Mieczkowski PA, Miller JP, Miller ML, Mills GB, Moiseenko F, Moore RA, Morris S, Morrison C, Morton D, Moschos S, Mose LE, Muller FL, Mungall AJ, Murawa D, Murawa P, Murray BA, Nezi L, Ng S, Nicholson D, Noble MS, Osunkoya A, Owonikoko TK, Ozenberger BA, Pagani E, Paklina OV, Pantazi A, Parfenov M, Parfitt J, Park PJ, Park WY, Parker JS, Passarelli F, Penny R, Perou CM, Pihl TD, Potapova O, Prieto VG, Protopopov A, Quinn MJ, Radenbaugh A, Rai K, Ramalingam SS, Raman AT, Ramirez NC, Ramirez R, Rao U, Rathmell WK, Ren X, Reynolds SM, Roach J, Robertson AG, Ross MI, Roszik J, Russo G, Saksena G, Saller C, Samuels Y, Sander C, Sander C, Sandusky G, Santoso N, Saul M, Saw RPM, Schadendorf D, Schein JE, Schultz N, Schumacher SE, Schwallier C, Scolyer RA, Seidman J, Sekhar PC, Sekhon HS, Senbabaoglu Y, Seth S, Shannon KF, Sharpe S, Sharpless NE, Shaw KRM, Shelton C, Shelton T, Shen R, Sheth M, Shi Y, Shiau CJ, Shmulevich I, Sica GL, Simons JV, Sinha R, Sipahimalani P, Sofia HJ, Soloway MG, Song X, Sougnez C, Spillane AJ, Spychała A, Stretch JR, Stuart J, Suchorska WM, Sucker A, Sumer SO, Sun Y, Synott M, Tabak B, Tabler TR, Tam A, Tan D, Tang J, Tarnuzzer R, Tarvin K, Tatka H, Taylor BS, Teresiak M, Thiessen N, Thompson JF, Thorne L, Thorsson V, Trent JM, Triche TJ Jr, Tsai KY, Tsou P, van den Berg DJ, van Allen EM, Veluvolu U, Verhaak RG, Voet D, Voronina O, Walter V, Walton JS, Wan Y, Wang Y, Wang Z, Waring S, Watson IR, Weinhold N, Weinstein JN, Weisenberger DJ, White P, Wilkerson MD, Wilmott JS, Wise L, Wiznerowicz M, Woodman SE, Wu CJ, Wu CC, Wu J, Wu Y, Xi R, Xu AW, Yang D, Yang L, Yang L, Zack TI, Zenklusen JC, Zhang H, Zhang J, Zhang W, Zhao X, Zhu J, Zhu K, Zimmer L, Zmuda E, Zou L (2015) Genomic classification of cutaneous melanoma. Cell 161:1681–1696. https://doi.org/10.1016/j.cell.2015.05.044 CrossRef Akbani R, Akdemir KC, Aksoy BA, Albert M, Ally A, Amin SB, Arachchi H, Arora A, Auman JT, Ayala B, Baboud J, Balasundaram M, Balu S, Barnabas N, Bartlett J, Bartlett P, Bastian BC, Baylin SB, Behera M, Belyaev D, Benz C, Bernard B, Beroukhim R, Bir N, Black AD, Bodenheimer T, Boice L, Boland GM, Bono R, Bootwalla MS, Bosenberg M, Bowen J, Bowlby R, Bristow CA, Brockway-Lunardi L, Brooks D, Brzezinski J, Bshara W, Buda E, Burns WR, Butterfield YSN, Button M, Calderone T, Cappellini GA, Carter C, Carter SL, Cherney L, Cherniack AD, Chevalier A, Chin L, Cho J, Cho RJ, Choi YL, Chu A, Chudamani S, Cibulskis K, Ciriello G, Clarke A, Coons S, Cope L, Crain D, Curley E, Danilova L, D’Atri S, Davidsen T, Davies MA, Delman KA, Demchok JA, Deng QA, Deribe YL, Dhalla N, Dhir R, DiCara D, Dinikin M, Dubina M, Ebrom JS, Egea S, Eley G, Engel J, Eschbacher JM, Fedosenko KV, Felau I, Fennell T, Ferguson ML, Fisher S, Flaherty KT, Frazer S, Frick J, Fulidou V, Gabriel SB, Gao J, Gardner J, Garraway LA, Gastier-Foster JM, Gaudioso C, Gehlenborg N, Genovese G, Gerken M, Gershenwald JE, Getz G, Gomez-Fernandez C, Gribbin T, Grimsby J, Gross B, Guin R, Gutschner T, Hadjipanayis A, Halaban R, Hanf B, Haussler D, Haydu LE, Hayes DN, Hayward NK, Heiman DI, Herbert L, Herman JG, Hersey P, Hoadley KA, Hodis E, Holt RA, Hoon DSB, Hoppough S, Hoyle AP, Huang FW, Huang M, Huang S, Hutter CM, Ibbs M, Iype L, Jacobsen A, Jakrot V, Janning A, Jeck WR, Jefferys SR, Jensen MA, Jones CD, Jones SJM, Ju Z, Kakavand H, Kang H, Kefford RF, Khuri FR, Kim J, Kirkwood JM, Klode J, Korkut A, Korski K, Krauthammer M, Kucherlapati R, Kwong LN, Kycler W, Ladanyi M, Lai PH, Laird PW, Lander E, Lawrence MS, Lazar AJ, Łaźniak R, Lee D, Lee JE, Lee J, Lee K, Lee S, Lee W, Leporowska E, Leraas KM, Li HI, Lichtenberg TM, Lichtenstein L, Lin P, Ling S, Liu J, Liu O, Liu W, Long GV, Lu Y, Ma S, Ma Y, Mackiewicz A, Mahadeshwar HS, Malke J, Mallery D, Manikhas GM, Mann GJ, Marra MA, Matejka B, Mayo M, Mehrabi S, Meng S, Meyerson M, Mieczkowski PA, Miller JP, Miller ML, Mills GB, Moiseenko F, Moore RA, Morris S, Morrison C, Morton D, Moschos S, Mose LE, Muller FL, Mungall AJ, Murawa D, Murawa P, Murray BA, Nezi L, Ng S, Nicholson D, Noble MS, Osunkoya A, Owonikoko TK, Ozenberger BA, Pagani E, Paklina OV, Pantazi A, Parfenov M, Parfitt J, Park PJ, Park WY, Parker JS, Passarelli F, Penny R, Perou CM, Pihl TD, Potapova O, Prieto VG, Protopopov A, Quinn MJ, Radenbaugh A, Rai K, Ramalingam SS, Raman AT, Ramirez NC, Ramirez R, Rao U, Rathmell WK, Ren X, Reynolds SM, Roach J, Robertson AG, Ross MI, Roszik J, Russo G, Saksena G, Saller C, Samuels Y, Sander C, Sander C, Sandusky G, Santoso N, Saul M, Saw RPM, Schadendorf D, Schein JE, Schultz N, Schumacher SE, Schwallier C, Scolyer RA, Seidman J, Sekhar PC, Sekhon HS, Senbabaoglu Y, Seth S, Shannon KF, Sharpe S, Sharpless NE, Shaw KRM, Shelton C, Shelton T, Shen R, Sheth M, Shi Y, Shiau CJ, Shmulevich I, Sica GL, Simons JV, Sinha R, Sipahimalani P, Sofia HJ, Soloway MG, Song X, Sougnez C, Spillane AJ, Spychała A, Stretch JR, Stuart J, Suchorska WM, Sucker A, Sumer SO, Sun Y, Synott M, Tabak B, Tabler TR, Tam A, Tan D, Tang J, Tarnuzzer R, Tarvin K, Tatka H, Taylor BS, Teresiak M, Thiessen N, Thompson JF, Thorne L, Thorsson V, Trent JM, Triche TJ Jr, Tsai KY, Tsou P, van den Berg DJ, van Allen EM, Veluvolu U, Verhaak RG, Voet D, Voronina O, Walter V, Walton JS, Wan Y, Wang Y, Wang Z, Waring S, Watson IR, Weinhold N, Weinstein JN, Weisenberger DJ, White P, Wilkerson MD, Wilmott JS, Wise L, Wiznerowicz M, Woodman SE, Wu CJ, Wu CC, Wu J, Wu Y, Xi R, Xu AW, Yang D, Yang L, Yang L, Zack TI, Zenklusen JC, Zhang H, Zhang J, Zhang W, Zhao X, Zhu J, Zhu K, Zimmer L, Zmuda E, Zou L (2015) Genomic classification of cutaneous melanoma. Cell 161:1681–1696. https://​doi.​org/​10.​1016/​j.​cell.​2015.​05.​044 CrossRef
4.
go back to reference Siroy AE, Boland GM, Milton DR, Roszik J, Frankian S, Malke J, Haydu L, Prieto VG, Tetzlaff M, Ivan D, Wang WL, Torres-Cabala C, Curry J, Roy-Chowdhuri S, Broaddus R, Rashid A, Stewart J, Gershenwald JE, Amaria RN, Patel SP, Papadopoulos NE, Bedikian A, Hwu WJ, Hwu P, Diab A, Woodman SE, Aldape KD, Luthra R, Patel KP, Shaw KR, Mills GB, Mendelsohn J, Meric-Bernstam F, Kim KB, Routbort MJ, Lazar AJ, Davies MA (2015) Beyond BRAFV600: clinical mutation panel testing by next-generation sequencing in advanced melanoma. J Invest Dermatol 135:508–515. https://doi.org/10.1038/jid.2014.366 CrossRefPubMed Siroy AE, Boland GM, Milton DR, Roszik J, Frankian S, Malke J, Haydu L, Prieto VG, Tetzlaff M, Ivan D, Wang WL, Torres-Cabala C, Curry J, Roy-Chowdhuri S, Broaddus R, Rashid A, Stewart J, Gershenwald JE, Amaria RN, Patel SP, Papadopoulos NE, Bedikian A, Hwu WJ, Hwu P, Diab A, Woodman SE, Aldape KD, Luthra R, Patel KP, Shaw KR, Mills GB, Mendelsohn J, Meric-Bernstam F, Kim KB, Routbort MJ, Lazar AJ, Davies MA (2015) Beyond BRAFV600: clinical mutation panel testing by next-generation sequencing in advanced melanoma. J Invest Dermatol 135:508–515. https://​doi.​org/​10.​1038/​jid.​2014.​366 CrossRefPubMed
7.
go back to reference Ascierto PA, Schadendorf D, Berking C, Agarwala SS, van Herpen CML, Queirolo P, Blank CU, Hauschild A, Beck JT, St-Pierre A, Niazi F, Wandel S, Peters M, Zubel A, Dummer R (2013) MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. Lancet Oncol 14:249–256. https://doi.org/10.1016/S1470-2045(13)70024-X CrossRefPubMed Ascierto PA, Schadendorf D, Berking C, Agarwala SS, van Herpen CML, Queirolo P, Blank CU, Hauschild A, Beck JT, St-Pierre A, Niazi F, Wandel S, Peters M, Zubel A, Dummer R (2013) MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. Lancet Oncol 14:249–256. https://​doi.​org/​10.​1016/​S1470-2045(13)70024-X CrossRefPubMed
8.
go back to reference Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, di Giacomo AM, Rutkowski P, del Vecchio M, Gutzmer R, Mandala M, Thomas L, Demidov L, Garbe C, Hogg D, Liszkay G, Queirolo P, Wasserman E, Ford J, Weill M, Sirulnik LA, Jehl V, Bozón V, Long GV, Flaherty K (2017) Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 18:435–445. https://doi.org/10.1016/S1470-2045(17)30180-8 CrossRefPubMed Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, di Giacomo AM, Rutkowski P, del Vecchio M, Gutzmer R, Mandala M, Thomas L, Demidov L, Garbe C, Hogg D, Liszkay G, Queirolo P, Wasserman E, Ford J, Weill M, Sirulnik LA, Jehl V, Bozón V, Long GV, Flaherty K (2017) Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 18:435–445. https://​doi.​org/​10.​1016/​S1470-2045(17)30180-8 CrossRefPubMed
10.
go back to reference Hodi FS, Corless CL, Giobbie-Hurder A, Fletcher JA, Zhu M, Marino-Enriquez A, Friedlander P, Gonzalez R, Weber JS, Gajewski TF, O'Day SJ, Kim KB, Lawrence D, Flaherty KT, Luke JJ, Collichio FA, Ernstoff MS, Heinrich MC, Beadling C, Zukotynski KA, Yap JT, van den Abbeele AD, Demetri GD, Fisher DE (2013) Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J Clin Oncol Off J Am Soc Clin Oncol 31:3182–3190. https://doi.org/10.1200/JCO.2012.47.7836 CrossRef Hodi FS, Corless CL, Giobbie-Hurder A, Fletcher JA, Zhu M, Marino-Enriquez A, Friedlander P, Gonzalez R, Weber JS, Gajewski TF, O'Day SJ, Kim KB, Lawrence D, Flaherty KT, Luke JJ, Collichio FA, Ernstoff MS, Heinrich MC, Beadling C, Zukotynski KA, Yap JT, van den Abbeele AD, Demetri GD, Fisher DE (2013) Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J Clin Oncol Off J Am Soc Clin Oncol 31:3182–3190. https://​doi.​org/​10.​1200/​JCO.​2012.​47.​7836 CrossRef
11.
go back to reference de Unamuno Bustos B, Murria Estal R, Pérez Simó G, de Juan Jimenez I, Escutia Muñoz B, Rodríguez Serna M, Alegre de Miquel V, Llavador Ros M, Ballester Sánchez R, Nagore Enguídanos E, Palanca Suela S, Botella Estrada R (2017) Towards personalized medicine in melanoma: implementation of a clinical next-generation sequencing panel. Sci Rep 7:495. https://doi.org/10.1038/s41598-017-00606-w CrossRefPubMedPubMedCentral de Unamuno Bustos B, Murria Estal R, Pérez Simó G, de Juan Jimenez I, Escutia Muñoz B, Rodríguez Serna M, Alegre de Miquel V, Llavador Ros M, Ballester Sánchez R, Nagore Enguídanos E, Palanca Suela S, Botella Estrada R (2017) Towards personalized medicine in melanoma: implementation of a clinical next-generation sequencing panel. Sci Rep 7:495. https://​doi.​org/​10.​1038/​s41598-017-00606-w CrossRefPubMedPubMedCentral
14.
go back to reference Carvajal RD, Sosman JA, Quevedo JF, Milhem MM, Joshua AM, Kudchadkar RR, Linette GP, Gajewski TF, Lutzky J, Lawson DH, Lao CD, Flynn PJ, Albertini MR, Sato T, Lewis K, Doyle A, Ancell K, Panageas KS, Bluth M, Hedvat C, Erinjeri J, Ambrosini G, Marr B, Abramson DH, Dickson MA, Wolchok JD, Chapman PB, Schwartz GK (2014) Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA 311:2397–2405. https://doi.org/10.1001/jama.2014.6096 CrossRefPubMedPubMedCentral Carvajal RD, Sosman JA, Quevedo JF, Milhem MM, Joshua AM, Kudchadkar RR, Linette GP, Gajewski TF, Lutzky J, Lawson DH, Lao CD, Flynn PJ, Albertini MR, Sato T, Lewis K, Doyle A, Ancell K, Panageas KS, Bluth M, Hedvat C, Erinjeri J, Ambrosini G, Marr B, Abramson DH, Dickson MA, Wolchok JD, Chapman PB, Schwartz GK (2014) Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA 311:2397–2405. https://​doi.​org/​10.​1001/​jama.​2014.​6096 CrossRefPubMedPubMedCentral
Metadata
Title
Comparison of targeted next generation sequencing (NGS) versus isolated BRAF V600E analysis in patients with metastatic melanoma
Authors
Meng-Lei Zhu
Lan Zhou
Navid Sadri
Publication date
01-09-2018
Publisher
Springer Berlin Heidelberg
Published in
Virchows Archiv / Issue 3/2018
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-018-2393-2

Other articles of this Issue 3/2018

Virchows Archiv 3/2018 Go to the issue