Mapping the Germline and Somatic Mutation Interaction Landscape in Indolent and Aggressive Prostate Cancers

Joint Authors

Wu, Jiande
Hicks, Chindo
Mamidi, Tarun Karthik Kumar

Source

Journal of Oncology

Issue

Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-15, 15 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2019-11-13

Country of Publication

Egypt

No. of Pages

15

Main Subjects

Diseases
Medicine

Abstract EN

Background.

A majority of prostate cancers (PCas) are indolent and cause no harm even without treatment.

However, a significant proportion of patients with PCa have aggressive tumors that progress rapidly to metastatic disease and are often lethal.

PCa develops through somatic mutagenesis, but emerging evidence suggests that germline genetic variation can markedly contribute to tumorigenesis.

However, the causal association between genetic susceptibility and tumorigenesis has not been well characterized.

The objective of this study was to map the germline and somatic mutation interaction landscape in indolent and aggressive tumors and to discover signatures of mutated genes associated with each type and distinguishing the two types of PCa.

Materials and Methods.

We integrated germline mutation information from genome-wide association studies (GWAS) with somatic mutation information from The Cancer Genome Atlas (TCGA) using gene expression data from TCGA on indolent and aggressive PCas as the intermediate phenotypes.

Germline and somatic mutated genes associated with each type of PCa were functionally characterized using network and pathway analysis.

Results.

We discovered gene signatures containing germline and somatic mutations associated with each type and distinguishing the two types of PCa.

We discovered multiple gene regulatory networks and signaling pathways enriched with germline and somatic mutations including axon guidance, RAR, WINT, MSP-RON, STAT3, PI3K, TR/RxR, and molecular mechanisms of cancer, NF-kB, prostate cancer, GP6, androgen, and VEGF signaling pathways for indolent PCa and MSP-RON, axon guidance, RAR, adipogenesis, and molecular mechanisms of cancer and NF-kB signaling pathways for aggressive PCa.

Conclusion.

The investigation revealed germline and somatic mutated genes associated with indolent and aggressive PCas and distinguishing the two types of PCa.

The study revealed multiple gene regulatory networks and signaling pathways dysregulated by germline and somatic alterations.

Integrative analysis combining germline and somatic mutations is a powerful approach to mapping germline and somatic mutation interaction landscape.

American Psychological Association (APA)

Mamidi, Tarun Karthik Kumar& Wu, Jiande& Hicks, Chindo. 2019. Mapping the Germline and Somatic Mutation Interaction Landscape in Indolent and Aggressive Prostate Cancers. Journal of Oncology،Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1184198

Modern Language Association (MLA)

Mamidi, Tarun Karthik Kumar…[et al.]. Mapping the Germline and Somatic Mutation Interaction Landscape in Indolent and Aggressive Prostate Cancers. Journal of Oncology No. 2019 (2019), pp.1-15.
https://search.emarefa.net/detail/BIM-1184198

American Medical Association (AMA)

Mamidi, Tarun Karthik Kumar& Wu, Jiande& Hicks, Chindo. Mapping the Germline and Somatic Mutation Interaction Landscape in Indolent and Aggressive Prostate Cancers. Journal of Oncology. 2019. Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1184198

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-1184198