Journal of Pathology and Translational Medicine

Original Article

Founder BRCA1 mutations in Nepalese population: Anurag Mehta, Himanshi Diwan, Garima Gupta, Shrinidhi Nathany, Shalini Agnihotri, Surender Dhanda; J Pathol Transl Med. 2022;56(4):212-216. Published online June 15, 2022; DOI: https://doi.org/10.4132/jptm.2022.05.02

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Background
Founder mutation is a heritable genetic alteration observed with high frequency in a geographically and culturally isolated population where one or more ancestors becomes the forebearer of the altered gene. The current study reports two founder mutations in the BRCA1 gene in the Nepalese people.
Methods
Germline BRCA testing in all surface epithelial ovarian cancers and the selected case of breast, prostate, and pancreatic cancers has been the standard practice from 2016 to 2021. One thousand one hundred thirtythree probands were screened for germline BRCA variants by next generation sequencing. The variants were classified as per the American Society of Medical Genetics and Genomics recommendations. Pathogenic (class V) and likely pathogenic (class IV) were considered clinically relevant and utilized for cascade screening.
Results
Nepalese population made up a subcohort of 5.12% (58/1,133) of probands tested for germline BRCA1/2 variants. Twenty-seven of these 58 tested harbored pathogenic genetic alterations in BRCA1/2 genes, with 23 being BRCA1 mutant. Sixteen of 23 BRCA1 mutant cases shared one common pathogenic mutation c.2214_2215insT (p.Lys739Ter) (NM_007294.4). Additionally, a second highly recurrent mutation in BRCA1 gene c.5068A>T (p.Lys1690Ter) (NM_007294.4) was noted in six patients from this population.
Conclusions
The overwhelming abundance of the above two variants in a geographically confined population confers these two genetic alterations a status of founder mutations amongst the people of Nepal. A more extensive population-based study to reaffirm these findings will help establish a dual site-specific germline testing similar to the “Multisite-3-assay” in Ashkenazi Jews as the primary screening tool, especially in a resource-constrained environment.

Citations

Citations to this article as recorded by

Hiding in plain sight: a partial deletion ofBRCA1exon 7 undetectable by MLPA is a Nepali founder variant
Virginia Clowes, Jenny C Taylor, Alistair T Pagnamenta
Journal of Medical Genetics.2024; : jmg-2024-110422. CrossRef
Finding significance: New perspectives in variant classification of the RAD51 regulators, BRCA2 and beyond
Hayley L. Rein, Kara A. Bernstein
DNA Repair.2023; 130: 103563. CrossRef
Digital PCR as a Highly Sensitive Diagnostic Tool: A Review
K. V. Kopylova, Ed. W. Kasparov, I. V. Marchenko, M. V. Smolnikova
Molecular Biology.2023; 57(5): 793. CrossRef
Digital PCR as a Highly Sensitive Diagnostic Tool: a Review
K. V. Kopylova, Ed. W. Kasparov, I. V. Marchenko, M. V. Smolnikova
Молекулярная биология.2023; 57(5): 771. CrossRef

Case Study

TTF1-positive SMARCA4/BRG1 deficient lung adenocarcinoma: Anurag Mehta, Himanshi Diwan, Divya Bansal, Manoj Gupta; J Pathol Transl Med. 2022;56(1):53-56. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.09.16

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182 Download
4 Web of Science
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Abstract PDF

SMARCA4/BRG1-deficient lung adenocarcinoma (SD-LUAD) is being recognized as a distinct subtype based on subtle differences in its clinical, morphological, and immunophenotypic attributes compared to other non–small cell lung carcinomas. We present here a case of SD-LUAD with curious thyroid transcription factor 1 (TTF1) expression in a morphologically heterogenous lung adenocarcinoma. The better differentiated area showed preservation of TTF1 expression, and a poorly differentiated tumor had loss of TTF1 expression with universal BRG1 loss.

Citations

Citations to this article as recorded by

One Case of Non-Small Cell Lung Cancer with SMARCA4 Deletion Was Reported
允龙宋
Medical Diagnosis.2024; 14(01): 137. CrossRef
Delineation of a SMARCA4-specific competing endogenous RNA network and its function in hepatocellular carcinoma
Lei Zhang, Ting Sun, Xiao-Ye Wu, Fa-Ming Fei, Zhen-Zhen Gao
World Journal of Clinical Cases.2022; 10(29): 10501. CrossRef
Novel germline SMARCA4 mutation in Small Cell Carcinoma of the Ovary, Hypercalcemic Type
Anurag Mehta, Himanshi Diwan, Diksha Karki, Divya Bansal, Meenakshi Kamboj, Anila Sharma, Shrinidhi Nathany, Sakshi Mattoo, Dushyant Kumar
Current Problems in Cancer: Case Reports.2022; 8: 100205. CrossRef

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