Discrepancies in tumor mutation burden reporting from sequential endobronchial ultrasound transbronchial needle aspiration samples within single lymph node stations - brief report

Frontiers in Oncology

Oncology

Carl Pahoff¹  Michael Bint²  Kimberley Ryan³  Jung Hwa Son³  Farzad Bashirzadeh³  David Fielding⁴  David Fairbairn⁵  Alan Hodgson⁵  Lakshmy Nandakumar⁵  Nicola Waddell⁶  Ann-Marie Patch⁶  John V. Pearson⁶  Gunter Hartel⁶  Vanessa Lakis⁶  Stephen H. Kazakoff⁶  Sowmya Sharma⁷  Katia Nones⁸  Peter T. Simpson⁹  Andrew J. Dalley⁹  Haarika Chittoory⁹  Kaltin Ferguson⁹  Sunil R. Lakhani^1,10  Mahendra Singh^1,10 

[1] Department of Respiratory Medicine, Gold Coast University Hospital, Southport, QLD, Australia;Department of Thoracic Medicine, Sunshine Coast University Hospital, Birtinya, QLD, Australia;Department of Thoracic Medicine, The Royal Brisbane & Women’s Hospital, Brisbane, QLD, Australia;Department of Thoracic Medicine, The Royal Brisbane & Women’s Hospital, Brisbane, QLD, Australia;UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia;Pathology Queensland, The Royal Brisbane & Women’s Hospital, Brisbane, QLD, Australia;QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia;QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia;ACL Pathology, Sydney, NSW, Australia;QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia;School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia;UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia;UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia;Pathology Queensland, The Royal Brisbane & Women’s Hospital, Brisbane, QLD, Australia;

关键词: endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA);    lung cancer;    cytology;    TSO500;    molecular diagnostics;    tumor mutation burden;   

DOI  :  10.3389/fonc.2023.1259882

 received in 2023-07-17, accepted in 2023-09-29,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionTumour Mutation Burden (TMB) is a potential biomarker for immune cancer therapies. Here we investigated parameters that might affect TMB using duplicate cytology smears obtained from endobronchial ultrasound transbronchial needle aspiration (EBUS TBNA)-sampled malignant lymph nodes.MethodsIndividual Diff-Quik cytology smears were prepared for each needle pass. DNA extracted from each smear underwent sequencing using large gene panel (TruSight Oncology 500 (TSO500 - Illumina)). TMB was estimated using the TSO500 Local App v. 2.0 (Illumina).ResultsTwenty patients had two or more Diff-Quik smears (total 45 smears) which passed sequencing quality control. Average smear TMB was 8.7 ± 5.0 mutations per megabase (Mb). Sixteen of the 20 patients had paired samples with minimal differences in TMB score (average difference 1.3 ± 0.85). Paired samples from 13 patients had concordant TMB (scores below or above a threshold of 10 mutations/Mb). Markedly discrepant TMB was observed in four cases, with an average difference of 11.3 ± 2.7 mutations/Mb. Factors affecting TMB calling included sample tumour content, the amount of DNA used in sequencing, and bone fide heterogeneity of node tumour between paired samples.ConclusionTMB assessment is feasible from EBUS-TBNA smears from a single needle pass. Repeated samples of a lymph node station have minimal variation in TMB in most cases. However, this novel data shows how tumour content and minor change in site of node sampling can impact TMB. Further study is needed on whether all node aspirates should be combined in 1 sample, or whether testing independent nodes using smears is needed.

【 授权许可】

Unknown   
Copyright © 2023 Fielding, Dalley, Singh, Nandakumar, Lakis, Chittoory, Fairbairn, Patch, Kazakoff, Ferguson, Bashirzadeh, Bint, Pahoff, Son, Ryan, Hodgson, Sharma, Pearson, Waddell, Lakhani, Hartel, Simpson and Nones