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CDKN2A/P16INK4A variants association with breast cancer and their in-silico analysis

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Abstract

CDKN2A was first identified as melanoma predisposition tumour suppressor gene and has been successively studied. The previous researches have not established any noteworthy association with breast cancer. Therefore, through extensive literature search and in-silico analysis, we have tried to focus on the role of CDKN2A in breast cancer. CDKN2A variants in breast cancer were collected from different databases. The overall percentage of variants (approximately 5.8%) and their incidence frequency in breast cancer cases were found to be very low as compared to the number of samples screened in different studies. Exon 2 was identified as the major region of alternations. Approximately 42.8% were entire gene deletions, while 24.2% were missense mutations. These variants cannot be ignored because of their pathogenic effects as interpreted by the bioinformatics tools used in the present study. Earlier studies have shown that CDKN2A excludes the predisposition of germline variants, but interestingly shares common breast cancer germline variants with other carcinomas. Most of the data have revealed this gene as rarely mutated or deleted in breast cancer. However, few association studies have shown that in addition to being a ‘multiple’ tumour suppressor gene, it is mutated/deleted more in breast cancer cell lines as compared to breast cancer tissues or blood samples; thus, this gene cannot be neglected as a breast cancer candidate gene. The deletion/malfunctioning of CDKN2A in different tumours including breast cancer has recently led to the discovery of many clinical CDK inhibitors. Furthermore, these collected genetic variants will also be helpful in developing diagnostic, preventive, and treatment approaches for patients.

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Authors and Affiliations

  1. Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad, 44000, Pakistan

    Ayesha Aftab, Samra Irum & Sobia Tabassum

  2. Genomics Research Lab, Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad, 44000, Pakistan

    Shaheen Shahzad

  3. The CAS Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, Anhui, China

    Hafiz Muhammad Jafar Hussain & Ranjha Khan

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  1. Ayesha Aftab
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Aftab, A., Shahzad, S., Hussain, H.M.J. et al. CDKN2A/P16INK4A variants association with breast cancer and their in-silico analysis. Breast Cancer 26, 11–28 (2019). https://doi.org/10.1007/s12282-018-0894-0

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