MTP10-01: Impact of genomic changes on the treatment of lung cancer

Small cell lung cancer (SCLC) is one of the severe malignancies with high mortality. Surgically resected tumor tissues from 50 Chinese SCLC patients were collected for next-generation sequencing to detect 520 cancer‐related genes. The most frequently altered genes were TP53 (94.0%), RB1 (86.0%), LRP1B (44.0%), SPTA1 (26.0%) and KMT2D (24.0%). We detected that NOTCH2, JAK2 and CDK12 (P<0.05) had a significantly higher mutation frequency in Chinese SCLC compared to the Cologne and MSKCC. The single nucleotide variation (SNV) is dominated by C>A (34.1%). We found a significant association between TMB-H (≥10.3muts/Mb) and ATM (P=0.023), CREBBP (P=0.010), KMT2D(P=0.050) and LRP1B (P=0.005) gene mutations in Chinese SCLC patients. Immunostaining was performed using the following antibodies: TTF-1, CgA, CD56, Syn, and Ki-67. Correlation analysis between the expression of 6 markers and mutations in signaling pathways showed that Syn and CgA expression were associated with 4 (cGMP-PKG, Chemokine, TGF-β and Phospholipase D) and 2 (cGMP-PKG and Phosphatidylinositol) signaling pathway mutations. Kaplan-Meier curve showed that age<55 years, mutant ARID2 and high TMB (≥7muts/Mb) were associated with a better prognosis, while the prognosis of patients with mutations in the Ras pathway was significantly improved. High TMB is an important prognostic factor for SCLC patients showed by multivariate analysis. In the combined cohort composed of current and two previous studies, survival analysis showed that SCLC patients with mutant LRP1B demonstrated better OS (P=0.0017). Patients with a high TMB (≥7muts/Mb) have a better prognosis (P=0.0053), consistent with our results in the Chinese cohort. We characterized the genomic alterations profile of Chinese SCLC patients and analyzed the correlation between genomic changes and immunohistochemical phenotypes at the signaling pathway level. Our data might provide useful information in the diagnosis and treatment for Chinese SCLC patients.

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Chromosomal and genomic changes in lung cancer

Cell Adhesion & Migration ◽

10.4161/cam.4.1.10884 ◽

2010 ◽

Vol 4 (1) ◽

pp. 100-106 ◽

Cited By ~ 20

Author(s):

Marileila Varella-Garcia

Keyword(s):

Lung Cancer ◽

Genomic Changes

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P2.01-075 Genomic Changes and Clinical Characteristics Associated with Wood-Smoke Exposure in Patients with Non-Small Cell Lung Cancer

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2017.09.1176 ◽

2017 ◽

Vol 12 (11) ◽

pp. S2097-S2098

Author(s):

N. Hernandez-Pedro ◽

G. Soca-Chafre ◽

C. Alaez ◽

K. Carrillo-Sanchez ◽

P. Barrios-Bernal ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Clinical Characteristics ◽

Small Cell ◽

Smoke Exposure ◽

Wood Smoke ◽

Small Cell Lung ◽

Genomic Changes

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The Impact of Genomic Changes on Treatment of Lung Cancer

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/rccm.201305-0843pp ◽

2013 ◽

Vol 188 (7) ◽

pp. 770-775 ◽

Cited By ~ 72

Author(s):

Stephanie Cardarella ◽

Bruce E. Johnson

Keyword(s):

Lung Cancer ◽

Genomic Changes ◽

The Impact

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Hidden Markov Model for Defining Genomic Changes in Lung Cancer Using Gene Expression Data

OMICS A Journal of Integrative Biology ◽

10.1089/omi.2006.10.276 ◽

2006 ◽

Vol 10 (3) ◽

pp. 276-288

Author(s):

Chiang-Ching Huang ◽

Jeremy M.G. Taylor ◽

David G. Beer ◽

Sharon L.R. Kardia

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Markov Model ◽

Hidden Markov Model ◽

Gene Expression Data ◽

Hidden Markov ◽

Expression Data ◽

Genomic Changes

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Complementary Sequential Circulating Tumor Cell (CTC) and Cell-Free Tumor DNA (ctDNA) Profiling Reveals Metastatic Heterogeneity and Genomic Changes in Lung Cancer and Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.698551 ◽

2021 ◽

Vol 11 ◽

Author(s):

Say Li Kong ◽

Xingliang Liu ◽

Swee Jin Tan ◽

Joyce A. Tai ◽

Ler Yee Phua ◽

...

Keyword(s):

Breast Cancer ◽

Lung Cancer ◽

Cancer Patients ◽

Primary Tumor ◽

Metastatic Tumor ◽

Amplicon Sequencing ◽

Breast Cancer Patients ◽

Genomic Changes ◽

The Impact ◽

Tumor Dna

IntroductionCirculating tumor cells (CTCs) and cell-free tumor DNA (ctDNA) are tumor components present in circulation. Due to the limited access to both CTC enrichment platforms and ctDNA sequencing in most laboratories, they are rarely analyzed together.MethodsConcurrent isolation of ctDNA and single CTCs were isolated from lung cancer and breast cancer patients using the combination of size-based and CD45-negative selection method via DropCell platform. We performed targeted amplicon sequencing to evaluate the genomic heterogeneity of CTCs and ctDNA in lung cancer and breast cancer patients.ResultsHigher degrees of genomic heterogeneity were observed in CTCs as compared to ctDNA. Several shared alterations present in CTCs and ctDNA were undetected in the primary tumor, highlighting the intra-tumoral heterogeneity of tumor components that were shed into systemic circulation. Accordingly, CTCs and ctDNA displayed higher degree of concordance with the metastatic tumor than the primary tumor. The alterations detected in circulation correlated with worse survival outcome for both lung and breast cancer patients emphasizing the impact of the metastatic phenotype. Notably, evolving genetic signatures were detected in the CTCs and ctDNA samples during the course of treatment and disease progression.ConclusionsA standardized sample processing and data analysis workflow for concurrent analysis of CTCs and ctDNA successfully dissected the heterogeneity of metastatic tumor in circulation as well as the progressive genomic changes that may potentially guide the selection of appropriate therapy against evolving tumor clonality.

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