Genomic Insights into Idiopathic Granulomatous Mastitis through Whole-Exome Sequencing: A Case Report of Eight Patients

Genomic Insights into Idiopathic Granulomatous Mastitis through Whole-Exome Sequencing: A Case Report of Eight Patients

International Journal of Molecular Sciences

10.3390/ijms25169058

http://dx.doi.org/10.3390/ijms25169058

Seeu Si Ong, Peh Joo Ho, Alexis Jiaying Khng, Benita Kiat Tee Tan, Qing Ting Tan, Ern Yu Tan, Su-Ming Tan, Thomas Choudary Putti, Swee Ho Lim, Ee Ling Serene Tang, Jingmei Li, Mikael Hartman

breast pathology, breast abscess, supprurative breast lesion, tuberculous mastitis, breast cancer, mastitis, idiopathic granulomatous mastitis, somatic mutations, pathogenic mutations, whole-exome sequencing

21 August 2024

Ong, S. S., Ho, P. J., Khng, A. J., Tan, B. K. T., Tan, Q. T., Tan, E. Y., Tan, S.-M., Putti, T. C., Lim, S. H., Tang, E. L. S., Li, J., & Hartman, M. (2024). Genomic Insights into Idiopathic Granulomatous Mastitis through Whole-Exome Sequencing: A Case Report of Eight Patients. International Journal of Molecular Sciences, 25(16), 9058. https://doi.org/10.3390/ijms25169058

Idiopathic granulomatous mastitis (IGM) is a rare condition characterised by chronic inflammation and granuloma formation in the breast. The aetiology of IGM is unclear. By focusing on the protein-coding regions of the genome, where most disease-related mutations often occur, whole-exome sequencing (WES) is a powerful approach for investigating rare and complex conditions, like IGM. We report WES results on paired blood and tissue samples from eight IGM patients. Samples were processed using standard genomic protocols. Somatic variants were called with two analytical pipelines: nf-core/sarek with Strelka2 and GATK4 with Mutect2. Our WES study of eight patients did not find evidence supporting a clear genetic component. The discrepancies between variant calling algorithms, along with the considerable genetic heterogeneity observed amongst the eight IGM cases, indicate that common genetic drivers are not readily identifiable. With only three genes, CHIT1, CEP170, and CTR9, recurrently altering in multiple cases, the genetic basis of IGM remains uncertain. The absence of validation for somatic variants by Sanger sequencing raises further questions about the role of genetic mutations in the disease. Other potential contributors to the disease should be explored.

Attribution 4.0 International (CC BY 4.0)

This research is supported by core funding from: Genome Institute of Singapore
Grant Reference no. : NA

This research / project is supported by the National University Health System - NA
Grant Reference no. : NUHSRO/2020/027/T1/Seed-Aug/11

This research / project is supported by the National Medical Research Council - NA
Grant Reference no. : NMRC/CSA-SI/0015/2017

This research / project is supported by the Yong Loo Lin School of Medicine - Breast Cancer Screening Prevention Programme
Grant Reference no. : NUHSRO/2020/121/BCSPP/LOA

Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

https://oar.a-star.edu.sg/communities-collections/articles/20840

1422-0067

Genome Institute of Singapore

https://www.mdpi.com/1422-0067/25/16/9058/pdf?version=1724313266