Dataset Information

Integrative genomic analyses of APOBEC-mutational signature, expression and germline deletion of APOBEC3 genes, and immunogenicity in multiple cancer types.

ABSTRACT: BACKGROUND:Although APOBEC-mutational signature is found in tumor tissues of multiple cancers, how a common germline APOBEC3A/B deletion affects the mutational signature remains unclear. METHODS:Using data from 10 cancer types generated as part of TCGA, we performed integrative genomic and association analyses to assess inter-relationship of expressions for isoforms APOBEC3A and APOBEC3B, APOBEC-mutational signature, germline APOBEC3A/B deletions, neoantigen loads, and tumor infiltration lymphocytes (TILs). RESULTS:We found that expression level of the isoform uc011aoc transcribed from the APOBEC3A/B chimera was associated with a greater burden of APOBEC-mutational signature only in breast cancer, while germline APOBEC3A/B deletion led to an increased expression level of uc011aoc in multiple cancer types. Furthermore, we found that the deletion was associated with elevated APOBEC-mutational signature, neoantigen loads and relative composition of T cells (CD8+) in TILs only in breast cancer. Additionally, we also found that APOBEC-mutational signature significantly contributed to neoantigen loads and certain immune cell abundances in TILs across cancer types. CONCLUSIONS:These findings reveal new insights into understanding the genetic, biological and immunological mechanisms through which APOBEC genes may be involved in carcinogenesis, and provide potential genetic biomarker for the development of disease prevention and cancer immunotherapy.

SUBMITTER: Chen Z

PROVIDER: S-EPMC6751822 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Integrative genomic analyses of APOBEC-mutational signature, expression and germline deletion of APOBEC3 genes, and immunogenicity in multiple cancer types.

Chen Zhishan Z Wen Wanqing W Bao Jiandong J Kuhs Krystle L KL Cai Qiuyin Q Long Jirong J Shu Xiao-Ou XO Zheng Wei W Guo Xingyi X

BMC medical genomics 20190918 1

<h4>Background</h4>Although APOBEC-mutational signature is found in tumor tissues of multiple cancers, how a common germline APOBEC3A/B deletion affects the mutational signature remains unclear.<h4>Methods</h4>Using data from 10 cancer types generated as part of TCGA, we performed integrative genomic and association analyses to assess inter-relationship of expressions for isoforms APOBEC3A and APOBEC3B, APOBEC-mutational signature, germline APOBEC3A/B deletions, neoantigen loads, and tumor infil ...[more]

PMID: 31533728

Similar Datasets

Project description:BackgroundLung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer (NSCLC) with poor survival in advanced stage. Nowadays the rate of nonsmoking patients has dramatically increased and may be associated with the presence of driver mutations. Better understanding of the mutation profile data of nonsmoking LUAD patients are critical to predict survival and provide greater benefits to more patients. The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC) has been shown to play an important role in molecular tumorigenesis of NSCLC. However, the clinical relevance of APOBEC in nonsmoking LUAD remains to be understood.MethodsLUAD patients with somatic mutation and RNA sequencing data obtained from The Cancer Genome Atlas (TCGA) were assessed and screened in the Gene Expression Omnibus. Transcriptome data and mutational signatures were analyzed using R package. Then, we used the least absolute shrinkage and selection operator (LASSO) regression model to construct the APOBEC3 score (APOBEC3 score) model. The prognostic value was evaluated using Kaplan-Meier analysis. Finally, the functional enrichment analysis of differential expressed genes (DEGs) and the immune-related features were also estimated using R package.ResultsBy analyzing the mutational profile data of NSCLC in the TCGA database, we found that different mutation patterns existed between smoking and nonsmoking patients, and the APOBEC3 family played an important role in the mutation pattern of nonsmoking patients with LUAD. We established an APOBEC3 score and found that TCW (W = A or T) mutation counts were significantly greater in the high APOBEC3 score group than in the low APOBEC3 score group. Furthermore, there were different immune feathers and prognostic values between the high and low APOBEC3 score patients, suggesting an independent prognostic factor of APOBEC3 in nonsmoking LUAD patients.ConclusionsWe established a comprehensive view of APOBEC3 mutations in nonsmoking LUAD patients. Our review provides new insights into using the APOBEC3 mutation to predict prognosis and improve the immunotherapy response for future applications.

Dataset Information

Integrative genomic analyses of APOBEC-mutational signature, expression and germline deletion of APOBEC3 genes, and immunogenicity in multiple cancer types.

Publications

Integrative genomic analyses of APOBEC-mutational signature, expression and germline deletion of APOBEC3 genes, and immunogenicity in multiple cancer types.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets