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MED12 somatic mutations encompassing exon 2 associated with benign breast fibroadenomas and not breast carcinoma in Indian women.
J Cell Biochem. 2019 01; 120(1):182-191.JC

Abstract

Fibroadenoma is the most common type of benign breast tumor, accounting for 90% of benign lesions in India. Somatic mutations in the mediator complex subunit 12 (MED12) gene play a critical role in fibroepithelial tumorigenesis. The current study evaluated the hotspot region encompassing exon 2 of the MED12 gene, in benign and malignant breast tumor tissue from women who presented for breast lump evaluation. A total of 100 (80 fibroadenoma and 20 breast cancer) samples were analyzed by polymerase chain reaction-Sanger sequencing. Sequence variant analysis showed that 68.75% of nucleotide changes were found in exon 2 and the remaining in the adjacent intron 1. Codon 44 was implicated as a hotspot mutation in benign tumors, and 86.36% of the identified mutations involved this codon. An in silico functional analysis of missense mutations using consensus scoring sorting intolerant from tolerant (SIFT), SIFT seq, Polyphen2, Mutation Assessor, SIFT transFIC, Polyphen2 transFIC, Mutation Assesor transFIC, I-Mutant, DUET, PON-PS, SNAP2, and protein variation effect analyzer] revealed that apart from variants involving codon 44 (G44S; G44H), others like V41A and E55D were also predicted to be deleterious. Most of the missense mutations appeared in the loop region of the MED12 protein, which is expected to affect its functional interaction with cyclin C-CDK8/CDK19, causing loss of mediator-associated cyclin depended kinase (CDK) activity. These results suggest a key role of MED12 somatic variations in the pathogenesis of fibroadenoma. For the first time, it was demonstrated that MED12 sequence variations are present in benign breast tumors in the south Indian population.

Authors+Show Affiliations

Department of Genetics and Molecular Medicine, Kamineni Hospitals, Hyderabad, India. Department of Genetics, Osmania University, Hyderabad, India.Department of Genetics and Molecular Medicine, Kamineni Hospitals, Hyderabad, India. Department of Biochemistry, Novel Global Community Educational Foundation, Hebersham, NSW, Australia.Department of Biochemistry, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.Department of Genetics, Osmania University, Hyderabad, India.Department of Pathology, Kamineni Hospitals, Hyderabad, India.Department of Radiology, Kamineni Academy of Medical Sciences and Research Centre, Hyderabad, India.Department of Oncology, Kamineni Hospitals, Hyderabad, India.Department of Oncology, Kamineni Hospitals, Hyderabad, India.Department of Genetics and Molecular Medicine, Kamineni Hospitals, Hyderabad, India. Department of Genetics and Molecular Medicine, Kamineni Hospitals, Narketpally, Telanga, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30230586

Citation

Darooei, Mina, et al. "MED12 Somatic Mutations Encompassing Exon 2 Associated With Benign Breast Fibroadenomas and Not Breast Carcinoma in Indian Women." Journal of Cellular Biochemistry, vol. 120, no. 1, 2019, pp. 182-191.
Darooei M, Khan F, Rehan M, et al. MED12 somatic mutations encompassing exon 2 associated with benign breast fibroadenomas and not breast carcinoma in Indian women. J Cell Biochem. 2019;120(1):182-191.
Darooei, M., Khan, F., Rehan, M., Zubeda, S., Jeyashanker, E., Annapurna, S., Shah, A., Maddali, S., & Hasan, Q. (2019). MED12 somatic mutations encompassing exon 2 associated with benign breast fibroadenomas and not breast carcinoma in Indian women. Journal of Cellular Biochemistry, 120(1), 182-191. https://doi.org/10.1002/jcb.27293
Darooei M, et al. MED12 Somatic Mutations Encompassing Exon 2 Associated With Benign Breast Fibroadenomas and Not Breast Carcinoma in Indian Women. J Cell Biochem. 2019;120(1):182-191. PubMed PMID: 30230586.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MED12 somatic mutations encompassing exon 2 associated with benign breast fibroadenomas and not breast carcinoma in Indian women. AU - Darooei,Mina, AU - Khan,Fazal, AU - Rehan,Mohd, AU - Zubeda,Syeda, AU - Jeyashanker,Erukambattu, AU - Annapurna,Srirambhatla, AU - Shah,Ashwin, AU - Maddali,Srinivas, AU - Hasan,Qurratulain, Y1 - 2018/09/19/ PY - 2018/03/02/received PY - 2018/06/26/accepted PY - 2018/9/20/pubmed PY - 2020/1/1/medline PY - 2018/9/20/entrez KW - Sanger sequencing KW - breast tumor KW - fibroadenoma (FA) KW - in silico analysis KW - mediator complex subunit 12 (MED12) gene KW - somatic mutation SP - 182 EP - 191 JF - Journal of cellular biochemistry JO - J. Cell. Biochem. VL - 120 IS - 1 N2 - Fibroadenoma is the most common type of benign breast tumor, accounting for 90% of benign lesions in India. Somatic mutations in the mediator complex subunit 12 (MED12) gene play a critical role in fibroepithelial tumorigenesis. The current study evaluated the hotspot region encompassing exon 2 of the MED12 gene, in benign and malignant breast tumor tissue from women who presented for breast lump evaluation. A total of 100 (80 fibroadenoma and 20 breast cancer) samples were analyzed by polymerase chain reaction-Sanger sequencing. Sequence variant analysis showed that 68.75% of nucleotide changes were found in exon 2 and the remaining in the adjacent intron 1. Codon 44 was implicated as a hotspot mutation in benign tumors, and 86.36% of the identified mutations involved this codon. An in silico functional analysis of missense mutations using consensus scoring sorting intolerant from tolerant (SIFT), SIFT seq, Polyphen2, Mutation Assessor, SIFT transFIC, Polyphen2 transFIC, Mutation Assesor transFIC, I-Mutant, DUET, PON-PS, SNAP2, and protein variation effect analyzer] revealed that apart from variants involving codon 44 (G44S; G44H), others like V41A and E55D were also predicted to be deleterious. Most of the missense mutations appeared in the loop region of the MED12 protein, which is expected to affect its functional interaction with cyclin C-CDK8/CDK19, causing loss of mediator-associated cyclin depended kinase (CDK) activity. These results suggest a key role of MED12 somatic variations in the pathogenesis of fibroadenoma. For the first time, it was demonstrated that MED12 sequence variations are present in benign breast tumors in the south Indian population. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/30230586/MED12_somatic_mutations_encompassing_exon_2_associated_with_benign_breast_fibroadenomas_and_not_breast_carcinoma_in_Indian_women_ L2 - https://doi.org/10.1002/jcb.27293 DB - PRIME DP - Unbound Medicine ER -