Genetic Alterations and Tumor Mutation Burden of Poorly Differentiated Small Cell Euro-endocrine Carcinomas are Similar in Lung Lesions and Distant Metastatic Foci

In recent years, Non-small cell lung cancer (NSCLC) has evolved into a prime example for precision oncology with multiple FDA-approved “precision” drugs. For the majority of NSCLC lacking targetable genetic alterations, immune checkpoint inhibition (ICI) has become standard of care in first-line treatment or beyond. PD-L1 tumor expression represents the only approved predictive biomarker for PD-L1/PD-1 checkpoint inhibition by therapeutic antibodies. Since PD-L1-negative or low-expressing tumors may also respond to ICI, additional factors are likely to contribute in addition to PD-L1 expression. Tumor mutation burden (TMB) has emerged as a potential candidate; however, it is the most complex biomarker so far and might represent a challenge for routine diagnostics. We therefore established a hybrid capture (HC) next-generation sequencing (NGS) assay that covers all oncogenic driver alterations as well as TMB and validated TMB values by correlation with the assay (F1CDx) used for the CheckMate 227 study. Results of the first consecutive 417 patients analyzed in a routine clinical setting are presented. Data show that fast reliable comprehensive diagnostics including TMB and targetable alterations are obtained with a short turn-around time. Thus, even complex biomarkers can easily be implemented in routine practice to optimize treatment decisions for advanced NSCLC.

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Blood tumor mutation burden can predict the clinical response to immune checkpoint inhibitors in advanced non-small cell lung cancer patients

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-02943-2 ◽

2021 ◽

Author(s):

Xi Chen ◽

Liangjie Fang ◽

Yanping Zhu ◽

Zhang Bao ◽

Qing Wang ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Small Cell ◽

Small Cell Lung ◽

Tumor Mutation Burden ◽

Lung Cancer Patients ◽

Mutation Burden

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Paired analysis of tumor mutation burden for lung adenocarcinoma and associated idiopathic pulmonary fibrosis

Scientific Reports ◽

10.1038/s41598-021-92098-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yasuto Yoneshima ◽

Eiji Iwama ◽

Shingo Matsumoto ◽

Taichi Matsubara ◽

Testuzo Tagawa ◽

...

Keyword(s):

Lung Cancer ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Adenocarcinoma ◽

Genetic Alterations ◽

Driver Mutations ◽

Somatic Variant ◽

Tumor Mutation Burden ◽

Mutation Burden ◽

And Oxidative Stress

AbstractGenetic alterations underlying the development of lung cancer in individuals with idiopathic pulmonary fibrosis (IPF) have remained unclear. To explore whether genetic alterations in IPF tissue contribute to the development of IPF-associated lung cancer, we here evaluated tumor mutation burden (TMB) and somatic variants in 14 paired IPF and tumor samples from patients with IPF-associated lung adenocarcinoma. We also determined TMB for 22 samples of lung adenocarcinoma from patients without IPF. TMB for IPF-associated lung adenocarcinoma was significantly higher than that for matched IPF tissue (median of 2.94 vs. 1.26 mutations/Mb, P = 0.002). Three and 102 somatic variants were detected in IPF and matched lung adenocarcinoma samples, respectively, with only one pair of specimens sharing one somatic variant. TMB for IPF-associated lung adenocarcinoma was similar to that for lung adenocarcinoma samples with driver mutations (median of 2.94 vs. 2.51 mutations/Mb) and lower than that for lung adenocarcinoma samples without known driver mutations (median of 2.94 vs. 5.03 mutations/Mb, P = 0.130) from patients without IPF. Our findings suggest that not only the accumulation of somatic mutations but other factors such as inflammation and oxidative stress might contribute to the development and progression of lung cancer in patients with IPF.

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