Literature DB >> 31028088

High Yield of RNA Sequencing for Targetable Kinase Fusions in Lung Adenocarcinomas with No Mitogenic Driver Alteration Detected by DNA Sequencing and Low Tumor Mutation Burden.

Ryma Benayed1, Michael Offin2, Kerry Mullaney1, Purvil Sukhadia1, Kelly Rios1, Patrice Desmeules3, Ryan Ptashkin1, Helen Won4, Jason Chang1, Darragh Halpenny5, Alison M Schram6, Charles M Rudin2,6,7, David M Hyman6, Maria E Arcila1, Michael F Berger1, Ahmet Zehir1, Mark G Kris2,6,7, Alexander Drilon2,6,7, Marc Ladanyi8.   

Abstract

PURPOSE: Targeted next-generation sequencing of DNA has become more widely used in the management of patients with lung adenocarcinoma; however, no clear mitogenic driver alteration is found in some cases. We evaluated the incremental benefit of targeted RNA sequencing (RNAseq) in the identification of gene fusions and MET exon 14 (METex14) alterations in DNA sequencing (DNAseq) driver-negative lung cancers. EXPERIMENTAL
DESIGN: Lung cancers driver negative by MSK-IMPACT underwent further analysis using a custom RNAseq panel (MSK-Fusion). Tumor mutation burden (TMB) was assessed as a potential prioritization criterion for targeted RNAseq.
RESULTS: As part of prospective clinical genomic testing, we profiled 2,522 lung adenocarcinomas using MSK-IMPACT, which identified 195 (7.7%) fusions and 119 (4.7%) METex14 alterations. Among 275 driver-negative cases with available tissue, 254 (92%) had sufficient material for RNAseq. A previously undetected alteration was identified in 14% (36/254) of cases, 33 of which were actionable (27 in-frame fusions, 6 METex14). Of these 33 patients, 10 then received matched targeted therapy, which achieved clinical benefit in 8 (80%). In the 32% (81/254) of DNAseq driver-negative cases with low TMB [0-5 mutations/Megabase (mut/Mb)], 25 (31%) were positive for previously undetected gene fusions on RNAseq, whereas, in 151 cases with TMB >5 mut/Mb, only 7% were positive for fusions (P < 0.0001).
CONCLUSIONS: Targeted RNAseq assays should be used in all cases that appear driver negative by DNAseq assays to ensure comprehensive detection of actionable gene rearrangements. Furthermore, we observed a significant enrichment for fusions in DNAseq driver-negative samples with low TMB, supporting the prioritization of such cases for additional RNAseq.See related commentary by Davies and Aisner, p. 4586. ©2019 American Association for Cancer Research.

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Year:  2019        PMID： 31028088      PMCID： PMC6679790          DOI： 10.1158/1078-0432.CCR-19-0225

Source DB:  PubMed          Journal:  Clin Cancer Res        ISSN： 1078-0432            Impact factor:   12.531


  64 in total

1.  Identification of KIF5B-RET and GOPC-ROS1 fusions in lung adenocarcinomas through a comprehensive mRNA-based screen for tyrosine kinase fusions.

Authors:  Yoshiyuki Suehara; Maria Arcila; Lu Wang; Adnan Hasanovic; Daphne Ang; Tatsuo Ito; Yuki Kimura; Alexander Drilon; Udayan Guha; Valerie Rusch; Mark G Kris; Maureen F Zakowski; Naiyer Rizvi; Raya Khanin; Marc Ladanyi
Journal:  Clin Cancer Res       Date:  2012-10-10       Impact factor: 12.531

2.  Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs.

Authors:  Mark G Kris; Bruce E Johnson; Lynne D Berry; David J Kwiatkowski; A John Iafrate; Ignacio I Wistuba; Marileila Varella-Garcia; Wilbur A Franklin; Samuel L Aronson; Pei-Fang Su; Yu Shyr; D Ross Camidge; Lecia V Sequist; Bonnie S Glisson; Fadlo R Khuri; Edward B Garon; William Pao; Charles Rudin; Joan Schiller; Eric B Haura; Mark Socinski; Keisuke Shirai; Heidi Chen; Giuseppe Giaccone; Marc Ladanyi; Kelly Kugler; John D Minna; Paul A Bunn
Journal:  JAMA       Date:  2014-05-21       Impact factor: 56.272

Review 3.  Repetitive DNA and next-generation sequencing: computational challenges and solutions.

Authors:  Todd J Treangen; Steven L Salzberg
Journal:  Nat Rev Genet       Date:  2011-11-29       Impact factor: 53.242

4.  Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations.

Authors:  Antonio Marchetti; Lara Felicioni; Sara Malatesta; Maria Grazia Sciarrotta; Luigi Guetti; Antonio Chella; Patrizia Viola; Carmela Pullara; Felice Mucilli; Fiamma Buttitta
Journal:  J Clin Oncol       Date:  2011-08-08       Impact factor: 44.544

5.  Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers.

Authors:  Snjezana Dogan; Ronglai Shen; Daphne C Ang; Melissa L Johnson; Sandra P D'Angelo; Paul K Paik; Edyta B Brzostowski; Gregory J Riely; Mark G Kris; Maureen F Zakowski; Marc Ladanyi
Journal:  Clin Cancer Res       Date:  2012-09-26       Impact factor: 12.531

6.  Identifying and targeting ROS1 gene fusions in non-small cell lung cancer.

Authors:  Kurtis D Davies; Anh T Le; Mariana F Theodoro; Margaret C Skokan; Dara L Aisner; Eamon M Berge; Luigi M Terracciano; Federico Cappuzzo; Matteo Incarbone; Massimo Roncalli; Marco Alloisio; Armando Santoro; D Ross Camidge; Marileila Varella-Garcia; Robert C Doebele
Journal:  Clin Cancer Res       Date:  2012-08-23       Impact factor: 12.531

Review 7.  The impact of translocations and gene fusions on cancer causation.

Authors:  Felix Mitelman; Bertil Johansson; Fredrik Mertens
Journal:  Nat Rev Cancer       Date:  2007-03-15       Impact factor: 60.716

Review 8.  Genome structural variation discovery and genotyping.

Authors:  Can Alkan; Bradley P Coe; Evan E Eichler
Journal:  Nat Rev Genet       Date:  2011-03-01       Impact factor: 53.242

9.  Integrative genomics viewer.

Authors:  James T Robinson; Helga Thorvaldsdóttir; Wendy Winckler; Mitchell Guttman; Eric S Lander; Gad Getz; Jill P Mesirov
Journal:  Nat Biotechnol       Date:  2011-01       Impact factor: 54.908

10.  Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration.

Authors:  Helga Thorvaldsdóttir; James T Robinson; Jill P Mesirov
Journal:  Brief Bioinform       Date:  2012-04-19       Impact factor: 11.622
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  109 in total

Review 1.  TRK Inhibitors in Non-Small Cell Lung Cancer.

Authors:  Guilherme Harada; Aline Bobato Lara Gongora; Cesar Martins da Costa; Fernando Costa Santini
Journal:  Curr Treat Options Oncol       Date:  2020-04-23

2.  TRK Fusions Are Enriched in Cancers with Uncommon Histologies and the Absence of Canonical Driver Mutations.

Authors:  Ezra Y Rosen; Debra A Goldman; Jaclyn F Hechtman; Ryma Benayed; Alison M Schram; Emiliano Cocco; Sophie Shifman; Yixiao Gong; Ritika Kundra; James P Solomon; Alberto Bardelli; Maurizio Scaltriti; Alexander Drilon; Alexia Iasonos; Barry S Taylor; David M Hyman
Journal:  Clin Cancer Res       Date:  2019-12-23       Impact factor: 12.531

3.  Molecular profiling and analysis of genetic aberrations aimed at identifying potential therapeutic targets in fibrolamellar carcinoma of the liver.

Authors:  Imane El Dika; Anita S Bowman; Michael F Berger; Marinela Capanu; Joanne F Chou; Ryma Benayed; Ahmet Zehir; Jinru Shia; Eileen M O'Reilly; David S Klimstra; David B Solit; Ghassan K Abou-Alfa
Journal:  Cancer       Date:  2020-07-14       Impact factor: 6.860

4.  MAPK Pathway Alterations Correlate with Poor Survival and Drive Resistance to Therapy in Patients with Lung Cancers Driven by ROS1 Fusions.

Authors:  Hiroki Sato; Adam J Schoenfeld; Evan Siau; Yue Christine Lu; Huichun Tai; Ken Suzawa; Daisuke Kubota; Allan J W Lui; Besnik Qeriqi; Marissa Mattar; Michael Offin; Masakiyo Sakaguchi; Shinichi Toyooka; Alexander Drilon; Neal X Rosen; Mark G Kris; David Solit; Elisa De Stanchina; Monika A Davare; Gregory J Riely; Marc Ladanyi; Romel Somwar
Journal:  Clin Cancer Res       Date:  2020-03-02       Impact factor: 12.531

Review 5.  New Targets in Lung Cancer (Excluding EGFR, ALK, ROS1).

Authors:  Alessandro Russo; Ana Rita Lopes; Michael G McCusker; Sandra Gimenez Garrigues; Giuseppina R Ricciardi; Katherine E Arensmeyer; Katherine A Scilla; Ranee Mehra; Christian Rolfo
Journal:  Curr Oncol Rep       Date:  2020-04-16       Impact factor: 5.075

6.  CNS Metastases in Patients With MET Exon 14-Altered Lung Cancers and Outcomes With Crizotinib.

Authors:  Michael Offin; Jia Luo; Robin Guo; John K Lyo; Christina Falcon; Jordan Dienstag; Olivia Wilkins; Jason Chang; Charles M Rudin; Gregory Riely; Natasha Rekhtman; Maria E Arcila; Glenn Heller; Marc Ladanyi; Bob T Li; Mark G Kris; Paul Paik; Alexander Drilon
Journal:  JCO Precis Oncol       Date:  2020-07-27

Review 7.  MET-dependent solid tumours - molecular diagnosis and targeted therapy.

Authors:  Robin Guo; Jia Luo; Jason Chang; Natasha Rekhtman; Maria Arcila; Alexander Drilon
Journal:  Nat Rev Clin Oncol       Date:  2020-06-08       Impact factor: 66.675

Review 8.  State-of-the-Art Strategies for Targeting RET-Dependent Cancers.

Authors:  Vivek Subbiah; Dong Yang; Vamsidhar Velcheti; Alexander Drilon; Funda Meric-Bernstam
Journal:  J Clin Oncol       Date:  2020-02-21       Impact factor: 44.544

9.  Targeted RNA expression profiling identifies high-grade endometrial stromal sarcoma as a clinically relevant molecular subtype of uterine sarcoma.

Authors:  Amir Momeni-Boroujeni; Nissreen Mohammad; Robert Wolber; Stephen Yip; Martin Köbel; Brendan C Dickson; Martee L Hensley; Mario M Leitao; Cristina R Antonescu; Ryma Benayed; Marc Ladanyi; Cheng-Han Lee; Sarah Chiang
Journal:  Mod Pathol       Date:  2020-10-19       Impact factor: 7.842

Review 10.  ROS1-dependent cancers - biology, diagnostics and therapeutics.

Authors:  Alexander Drilon; Chelsea Jenkins; Sudarshan Iyer; Adam Schoenfeld; Clare Keddy; Monika A Davare
Journal:  Nat Rev Clin Oncol       Date:  2020-08-05       Impact factor: 66.675
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