Identification of putative functional genes in breast and other cancers with potentially shared aetiology

Chandler, Stephen; Crea, Francesco; Hirst, Mark; Cox, Angela and Rigas, Sushilaben (2017). Identification of putative functional genes in breast and other cancers with potentially shared aetiology. In: The Human Genome in Healthcare, 23-24 Nov 2017, The Royal Society, London, UK.

Abstract

Breast cancer is the 2nd most common cancer globally with nearly 1.7 million new cases of all cancers in women (1 in 4). Sporadic breast cancers studies have very few identified functional variants that underlie breast with other cancers such as lung and bone. The aim of this study was to identify DNA/RNA variants within genes that function in the development of breast cancer and other cancers with putative shared aetiology.

Microarray datasets of primary breast cancer tissues were collected from the Gene Expression Omnibus (GEO). Tissue samples were categorised into histological and molecular subtypes. A total of 1638 histological and 1115 molecular breast cancer samples were compared to normal breast tissues 53 and 58 respectively using an empirical Bayes moderated t-test (P<0.01).

6,964 significantly expressed genes were identified in invasive ductal carcinoma (IDC), 6,867 ductal carcinoma in-situ (DCIS), 6,910 invasive lobular carcinoma (ILC), and 6,806 lobular carcinoma in-situ (LCIS). Within molecular subtypes 14,282 significantly expressed genes were identified in luminal A, 13,359 luminal B, 10,497 HER2, and 15,294 triple negative.

We identified; PTPRC, ATP6VOC, NREP, FAM114A1, GNB2, RAD1, ZMYND11, SLC50A1, PEAR1, NUF2, and SMC4 to be putative novel genes underlying breast cancer.

Many of the most significant genes identified in this study have been identified in other cancers (prostate, ovarian, colon, lung, and gastric) which may be due to underlying shared mechanisms in cancers. The potential of the genes identified may provide new biomarkers for diagnosis and treatment in breast and other cancers and pose potentially novel therapeutic treatments.

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