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.2025; 62(2): 54. 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

Review

Clinicopathological characteristics of BRCA-associated breast cancer in Asian patients: Eun-Kyu Kim, So Yeon Park, Sung-Won Kim; J Pathol Transl Med. 2020;54(4):265-275. Published online May 14, 2020; DOI: https://doi.org/10.4132/jptm.2020.04.07

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Abstract PDF

BRCA1/2 germline mutations account for the majority of hereditary breast cancers. Since the identification of the BRCA genes, several attempts have been made to define the clinicopathological characteristics of BRCA-associated breast cancer in comparison with sporadic breast cancer. Asians constitute 60% of the world population, and although the incidence of breast cancer in Asia remains low compared to the West, breast cancer is the most prevalent female cancer in the region. The epidemiological aspects of breast cancer are different between Asians and Caucasians. Asian patients present with breast cancer at a younger age than Western patients. The contributions of BRCA1/2 mutations to breast cancer incidence are expected to differ between Asians and Caucasians, and the different genetic backgrounds among races are likely to influence the breast cancer phenotypes. However, most large-scale studies on the clinicopathological characteristics of BRCA-associated breast cancer have been on Western patients, while studies on Asian populations were small and sporadic. In this review, we provide an overview of the clinical and pathological characteristics of BRCA-associated breast cancer, incorporating findings on Asian patients.

Citations

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Predicting BRCA mutation and stratifying targeted therapy response using multimodal learning: a multicenter study
Yi Li, Xiaomin Xiong, Xiaohua Liu, Mengke Xu, Boping Yang, Xiaoju Li, Yu Li, Bo Lin, Bo Xu
Annals of Medicine.2024;[Epub] CrossRef
Characteristics of breast cancer patients tested for germline BRCA1/2 mutations by next‐generation sequencing in Ramathibodi Hospital, Mahidol University
Songporn Oranratnachai, Watchalawalee Yamkaew, Atchara Tunteeratum, Thongchai Sukarayothin, Nareenart Iemwimangsa, Ravat Panvichien
Cancer Reports.2023;[Epub] CrossRef
Prognostic and predictive biomarkers with therapeutic targets in breast cancer: A 2022 update on current developments, evidence, and recommendations
Clement Chung, Vanessa T.Y. Yeung, Kenneth C.W. Wong
Journal of Oncology Pharmacy Practice.2023; 29(6): 1343. CrossRef
Mutations of TP53 and genes related to homologous recombination repair in breast cancer with germline BRCA1/2 mutations
Jinyong Kim, Kyeonghun Jeong, Hyeji Jun, Kwangsoo Kim, Jeong Mo Bae, Myung Geun Song, Hanbaek Yi, Songyi Park, Go-un Woo, Dae-Won Lee, Tae-Yong Kim, Kyung-Hun Lee, Seock-Ah Im
Human Genomics.2023;[Epub] CrossRef
BRCA 1–2 Incidence in Synchronous and Metachronous Breast Cancer: a Tertiary Center Study
Ahmet Dağ, Bilal Arslan, Erkan Güler, Serdar Mermer
Indian Journal of Surgery.2022;[Epub] CrossRef
Habitat Analysis of Breast Cancer‐Enhanced MRI Reflects BRCA1 Mutation Determined by Immunohistochemistry
Tianming Du, Haidong Zhao, Chen Li
BioMed Research International.2022;[Epub] CrossRef
Prevalence and Factors Associated with BRCA1/2 Gene Mutation in Chinese Populations with Breast Cancer
Guoding Huang, Hongquan Lu, Qizhu Chen, Xinting Huang
International Journal of General Medicine.2022; Volume 15: 6783. CrossRef
Association between fertility treatments and breast cancer risk in women with a family history or BRCA mutations: a systematic review and meta-analysis
Xiaojing Liu, Jing Yue, Ruqiya Pervaiz, Hanwang Zhang, Lan Wang
Frontiers in Endocrinology.2022;[Epub] CrossRef
Relationship between Baseline [18F]FDG PET/CT Semiquantitative Parameters and BRCA Mutational Status and Their Prognostic Role in Patients with Invasive Ductal Breast Carcinoma
Francesco Dondi, Domenico Albano, Pietro Bellini, Luca Camoni, Giorgio Treglia, Francesco Bertagna
Tomography.2022; 8(6): 2662. CrossRef
The clinical and diagnostic characteristics of BRCA-associated breast cancer
M.A. Golotyuk, A.A. Berezhnoy, N.V. Kazantseva, A.V. Dorofeev, S.A. Shevchenko, I.V. Borzunov, N.I. Rozhkova
Onkologiya. Zhurnal imeni P.A.Gertsena.2022; 11(6): 18. CrossRef
The Clinical and Pathological Profile of BRCA1 Gene Methylated Breast Cancer Women: A Meta-Analysis
Ilary Ruscito, Maria Luisa Gasparri, Maria Paola De Marco, Flavia Costanzi, Aris Raad Besharat, Andrea Papadia, Thorsten Kuehn, Oreste Davide Gentilini, Filippo Bellati, Donatella Caserta
Cancers.2021; 13(6): 1391. CrossRef
Changing Patterns in Clinicopathological Characteristics of Breast Cancer and Prevalence of BRCA Mutations: Analysis in a Rural Area of Southern China
Qiuming Wang, Heming Wu, Yongquan Lan, Jinhong Zhang, Jingna Wu, Yunuo Zhang, Liang Li, Donghua Liu, Jinfeng Zhang
International Journal of General Medicine.2021; Volume 14: 7371. CrossRef

Original Article

Allelic Loss at the BRCA1 and BRCA2 Loci in Sporadic Breast Carcinoma Using Paraffin Embedded Tissue .: Ji Young Park, Myung Hoon Lee, Dong Ja Kim, Tae In Park, Young Ha Lee, Jung Wan Kim, Yoon Kyung Sohn; Korean J Pathol. 2002;36(2):100-105.

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Abstract PDF: BACKGROUND
Germline mutations in the breast cancer-associated genes BRCA1 and BRCA2 confer susceptibility and a lifetime risk of breast. Several morphological and clinical features have been attributed to hereditary tumors. However, in sporadic breast cancer, the interrelationship between the loss of heterozygosity (LOH) of these loci and clinical features remains to be fully elucidated.
METHODS
Microdissected paraffin-embedded tissue blocks of 48 cases of surgically resected breast carcinoma were investigated to identify the LOH of BRCA1 and BRCA2 using microsatellite markers.
RESULTS
Of 48 cases, 22 (45.9%) exhibited LOH at BRCA1 locus while in 29 out of 48 (60.4%) cases LOH was observed for the BRCA2 region. There was no significant correlation between LOH at BRCA1/2 and the patient's age, tumor size, histologic grade or lymph node metastasis. When comparing the frequency of LOH with the expression of several prognostic factors, such as p53, c-erb B2 protein, estrogen and progesterone receptor using immunohistochemical stain, there was only correlation with LOH at BRCA2 and the progesterone receptor.
CONCLUSIONS
Our results suggest that allelic deletion play a role to the development of sporadic breast cancers.

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