EGFR T790M mutation MALDI-TOF mass spectrometry droplet digital PCR (ddPCR) real time quantitative PCR (AS-PCR) ultra-deep next generation sequencing (NGS)

Journal

Translational lung cancer research
ISSN: 2218-6751
Titre abrégé: Transl Lung Cancer Res
Pays: China
ID NLM: 101646875

Informations de publication

Date de publication:
Oct 2019
Historique:
entrez: 19 11 2019
pubmed: 19 11 2019
medline: 19 11 2019
Statut: ppublish

Résumé

Routine testing of baseline We compared the diagnostic performance, sensitivity and specificity of three methods, namely MALDI-TOF mass spectrometry (MS), Allele-Specific Real Time PCR (AS-PCR), droplet digital PCR (ddPCR). Ultra-deep next generation sequencing (NGS) validation of T790M-mutant NSCLCs was performed using SiRe Baseline T790M occurred in 17% of the tumors. Intermediately sensitive techniques such as MALDI-TOF MS (detection limit of T790M ≥5%) allow to detect T790M in 2% of cases exhibiting mutant-allele fractions ranging from 11.5% to 17%. Median overall survival (OS) in these patients was poor (7.3 months) and progression free survival (PFS) was of 3.3 months in patients treated with a 1st generation EGFR TKI. The remaining T790M-positive cases showed very low mutant-allele fractions ranging from 0.07% to 0.38% and required highly sensitive methods such as ddPCR and NGS to be identified. All these cases showed a concurrent sensitizing Routine test of baseline

Sections du résumé

BACKGROUND BACKGROUND
Routine testing of baseline
METHODS METHODS
We compared the diagnostic performance, sensitivity and specificity of three methods, namely MALDI-TOF mass spectrometry (MS), Allele-Specific Real Time PCR (AS-PCR), droplet digital PCR (ddPCR). Ultra-deep next generation sequencing (NGS) validation of T790M-mutant NSCLCs was performed using SiRe
RESULTS RESULTS
Baseline T790M occurred in 17% of the tumors. Intermediately sensitive techniques such as MALDI-TOF MS (detection limit of T790M ≥5%) allow to detect T790M in 2% of cases exhibiting mutant-allele fractions ranging from 11.5% to 17%. Median overall survival (OS) in these patients was poor (7.3 months) and progression free survival (PFS) was of 3.3 months in patients treated with a 1st generation EGFR TKI. The remaining T790M-positive cases showed very low mutant-allele fractions ranging from 0.07% to 0.38% and required highly sensitive methods such as ddPCR and NGS to be identified. All these cases showed a concurrent sensitizing
CONCLUSIONS CONCLUSIONS
Routine test of baseline

Identifiants

pubmed: 31737495
doi: 10.21037/tlcr.2019.09.18
pii: tlcr-08-05-584
pmc: PMC6835109
doi:

Types de publication

Journal Article

Langues

eng

Pagination

584-592

Commentaires et corrections

Type : CommentIn

Informations de copyright

2019 Translational Lung Cancer Research. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of Interest: The authors have no conflicts of interest to declare.

Références

Oncotarget. 2017 Oct 12;8(58):98384-98393
pubmed: 29228697
Clin Cancer Res. 2011 Mar 1;17(5):1169-80
pubmed: 21248300
Clin Cancer Res. 2011 Mar 1;17(5):1160-8
pubmed: 21233402
J Clin Pathol. 2019 Jan;72(1):38-45
pubmed: 30279174
Clin Cancer Res. 2013 Apr 15;19(8):2240-7
pubmed: 23470965
N Engl J Med. 2018 Jan 11;378(2):113-125
pubmed: 29151359
Annu Rev Med. 2008;59:429-42
pubmed: 17716025
Nat Genet. 2005 Dec;37(12):1315-6
pubmed: 16258541
Ann Oncol. 2014 Feb;25(2):423-8
pubmed: 24478319
Transl Lung Cancer Res. 2018 Apr;7(Suppl 2):S127-S130
pubmed: 29782562
Lung Cancer. 2016 Apr;94:46-53
pubmed: 26973206
Lung Cancer. 2017 Jun;108:83-89
pubmed: 28625654
Clin Cancer Res. 2014 Dec 1;20(23):5898-907
pubmed: 25303979
J Clin Oncol. 2008 May 20;26(15):2442-9
pubmed: 18458038
J Clin Oncol. 2012 Feb 1;30(4):433-40
pubmed: 22215752
Lancet Respir Med. 2017 May;5(5):435-444
pubmed: 28408243
Clin Cancer Res. 2014 Apr 1;20(7):2001-10
pubmed: 24493829
J Clin Oncol. 2006 Apr 10;24(11):1700-4
pubmed: 16505411
Sci Transl Med. 2011 Mar 23;3(75):75ra26
pubmed: 21430269
Br J Cancer. 2017 Mar 14;116(6):802-810
pubmed: 28170370
Lung Cancer. 2017 Aug;110:7-13
pubmed: 28676222
N Engl J Med. 2008 Jul 24;359(4):366-77
pubmed: 18596266
Clin Cancer Res. 2011 Jun 1;17(11):3812-21
pubmed: 21531810
Lancet Oncol. 2012 Mar;13(3):239-46
pubmed: 22285168
J Thorac Oncol. 2012 Nov;7(11):1640-4
pubmed: 22899358
J Thorac Oncol. 2015 Sep;10(9):1243-1260
pubmed: 26291008
J Thorac Dis. 2018 Apr;10(4):2311-2320
pubmed: 29850136

Auteurs

Lucio Lettig (L)

Unit of Pathology, Department of Medicine and Surgery, ASST Sette Laghi, University of Insubria, Varese, Italy.

Nora Sahnane (N)

Unit of Pathology, Department of Medicine and Surgery, ASST Sette Laghi, University of Insubria, Varese, Italy.

Francesco Pepe (F)

Department of Public Health, University of Naples Federico II, Naples, Italy.

Roberta Cerutti (R)

Unit of Pathology, Department of Medicine and Surgery, ASST Sette Laghi, University of Insubria, Varese, Italy.

Chiara Albeni (C)

Unit of Pathology, Department of Medicine and Surgery, ASST Sette Laghi, University of Insubria, Varese, Italy.

Francesca Franzi (F)

Unit of Pathology, Department of Medicine and Surgery, ASST Sette Laghi, University of Insubria, Varese, Italy.

Giovanni Veronesi (G)

Research Center in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery, University of Insubria, Varese, Italy.

Francesca Ogliari (F)

Unit of Oncology, ASST Sette Laghi, Varese, Italy.

Alessia Pastore (A)

Unit of Oncology, ASST Sette Laghi, Varese, Italy.

Alessandro Tuzi (A)

Unit of Oncology, ASST Sette Laghi, Varese, Italy.

Graziella Pinotti (G)

Unit of Oncology, ASST Sette Laghi, Varese, Italy.

Antonella Bovio (A)

Unit of Oncology, ASST Valle Olona, Varese, Italy.

Claudio Verusio (C)

Unit of Oncology, ASST Valle Olona, Varese, Italy.

Monica Giordano (M)

Unit of Oncology, ASST Lariana, Como, Italy.

Giancarlo Troncone (G)

Department of Public Health, University of Naples Federico II, Naples, Italy.

Fausto Sessa (F)

Unit of Pathology, Department of Medicine and Surgery, ASST Sette Laghi, University of Insubria, Varese, Italy.

Umberto Malapelle (U)

Department of Public Health, University of Naples Federico II, Naples, Italy.

Daniela Furlan (D)

Unit of Pathology, Department of Medicine and Surgery, ASST Sette Laghi, University of Insubria, Varese, Italy.

Classifications MeSH