Abstract 4735
Background
Lung cancer incidence and mortality could be influenced by altitude. In Tibet population Lung cancer was reported to be the sixth deadly malignant cancer, compared with the first deadly tumor in mainland of China. This study is conducted to investigate the mutation profile of Tibet non-small cell lung cancer by whole-exome sequencing.
Methods
We enrolled 17 Tibetan lung cancer patients. Composing of seven adenocarcinomas (Tibetan-LUAD) and 10 squamous carcinomas (Tibetan-LUSC). Paired tissues from malignant tumors and normal lymph nodes were subjected to whole exome sequencing by Illumina X TEN platform using paired-end 150X strategy.
Results
Tibetan LUAD harbored less somatic mutations comparing to median number of somatic mutations detected in TCGA. EGFR mutated most frequently in Tibetan LUAD, but TP53 only mutated in two patients, one of which harbored EGFR mutation as well suggesting reduced responsiveness to first line EGFR-TKIs. Mutation burden of Tibetan-LUSC was similar with TCGA LUSC cohort. In Tibetan LUSC, eight patients carried TP53 mutations. Besides, C>A transversion ratio was lower in Tibetan population than in TCGA for both adenocarcinomas and squamous carcinomas. Mutational signature 1 and 4, which were defined in COSMIC to be related with aging and smoking, contributed largely in Tibetan NSCLC. Other mutational signatures related with failure of DNA double-strand break-repair by homologous recombination and AID/APOBEC cytidine deaminases activation were also noticed. In Tibetan LUAD, amplification in 18 cytobands with q value< 0.25 were remarked. Deletions in two cytoband regions (17p13.1 and 19q13.41) were detected and the q value were 0.025 and 0.056 respectively. For Tibetan-LUSC, amplifications in 22 cytoband regions were remarked with q value <0.25 and deletions were detected in eight cytoband regions with q value between 0.001 and 0.25.
Conclusions
We revealed different mutational landscape, including base substitution status, mutational signature, frequently mutated genes, between Tibetan NSCLC, Chinese Han NSCLC and TCGA NSCLC and provide some insights about the possible role of high-altitude environment on NSCLC and uncovered potential candidate genes for further investigation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Guowei Che.
Funding
Genetron Health (Beijing) Co. Ltd., Beijing, China.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4883 - A New Population Model Validated Pharmacokinetic Similarity of HLX01 and Rituximab in B-Cell Lymphoma
Presenter: Yuankai Shi
Session: Poster Display session 1
Resources:
Abstract
4908 - Efficacy of salvage therapy in the treatment of Helicobacter pylori-positive gastric low-grade mucosa-associated lymphoid tissue lymphoma
Presenter: Sung-Nam Lim
Session: Poster Display session 1
Resources:
Abstract
2360 - Mutational analysis of extranodal marginal zone lymphoma using next generation sequencing
Presenter: Seok Jae Huh
Session: Poster Display session 1
Resources:
Abstract
2430 - Clinical features, treatment and outcomes of colon and rectum mucosa-associated lymphoid tissue (MALT) lymphoma: Literature reviews published in English between 1993 and 2017
Presenter: Jeong Yeon Kim
Session: Poster Display session 1
Resources:
Abstract
4654 - Splenic marginal zone lymphoma: clinical characteristics and prognostic factors in a series of 52 patients
Presenter: Guldane Cengiz Seval
Session: Poster Display session 1
Resources:
Abstract
1732 - Safety and efficacy of Bendamustine and Rituximab (BR) regimen in Indian Chronic Lymphocytic Leukemia patients
Presenter: Ajay Gogia
Session: Poster Display session 1
Resources:
Abstract
5784 - N-terminal B-type natriuretic peptide (NT-proBNP) as an independed prognostic marker for patients with newly diagnosed multiple myeloma complicated by dialysis-dependent renal failure
Presenter: Sergey Semochkin
Session: Poster Display session 1
Resources:
Abstract
836 - The first-line effect of Bortezomib-based Therapy on Clinical Outcomes for Taiwanese Patients with multiple myeloma
Presenter: Ching-Liang Ho
Session: Poster Display session 1
Resources:
Abstract
2085 - Impact of Donor Lymphocyte Infusion in Relapsing Myeloid Neoplasms Post Allogeneic Hematopoietic Stem Cell Transplantation
Presenter: Hanafy Hafez
Session: Poster Display session 1
Resources:
Abstract
6079 - Invasive fungal diseases in patients with Hodgkin’s lymphoma before and after allogeneic hematopoietic stem cell transplantation
Presenter: Marina Popova
Session: Poster Display session 1
Resources:
Abstract