Mutational Landscape for Indian Hereditary Breast and Ovarian Cancer Cohort Suggests Need for Identifying Population Specific Genes and Biomarkers for Screening

Kadri, Mohammed Shaad N; Patel, Komal; Bhargava, Poonam; Shah, Franky D.; Badgujar, Nutan V.; Tarapara, Bhoomi; Patel, Prabhudas S; Shaikh, Mohammed Inayatullah; Shah, Krati; Patel, Apurva; Pandya, Shashank; Vora, Hemangini H.; Joshi, Chaitanya; Joshi, Madhvi

doi:10.3389/fonc.2020.568786

Cited by 12 publications

(15 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, we observed the c.220C > T (p.Gln74Ter) BRCA1 Mut in a TNBC patient. Interestingly, this variant was recently reported in a TNBC patient from North India [44]. This variant was also reported in Chinese breast cancer patients [39].…”

Section: Discussionmentioning

confidence: 54%

Analysis of pathogenic variants in BRCA1 and BRCA2 genes using next-generation sequencing in women with triple negative breast cancer from South India

et al. 2022

View full text Add to dashboard Cite

The frequency of triple-negative breast cancer (TNBC) incidence varies among different populations, suggesting the involvement of genetic component towards TNBC development. Previous studies have reported that BRCA1/2 germline mutations confer a lifetime risk of developing TNBC. However, there is hardly any information regarding the common pathogenic variants (PVs) in BRCA1/2 genes that contribute to TNBC in the Indian population. Hence, we screened for PVs in BRCA1/2 and their association with clinico-pathological features in TNBC patients. Among the 59 TNBC genomic DNA samples sequenced, 8 BRCA mutations were detected in 59 TNBC patients (13.6%). Almost 50% pre-menopausal TNBC patients had a BRCA mutation. Of the 8 BRCA mutations, we observed BRCA1 mutations in 6 TNBC patients, and BRCA2 mutations in 2 TNBC patients. Among the 6 BRCA1 mutations, three were c.68_69delAG (185delAG) mutation. Remarkably, all the TNBC patients with BRCA mutations exhibited higher-grade tumors (grade 2 or 3). However, among the BRCA mutation carriers, only one patient with a BRCA2 mutation (p.Glu1879Lys) developed metastasis in the observed cohort. Our data advocates that South Indian women with higher grade TNBC tumors and without hereditary breast and ovarian cancer should be considered for BRCA mutation screening, thereby enabling enhanced decision-making and preventive therapy.

show abstract

Section: Discussionmentioning

confidence: 54%

Analysis of pathogenic variants in BRCA1 and BRCA2 genes using next-generation sequencing in women with triple negative breast cancer from South India

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Frameshift or nonsense mutations that disrupt or eliminate the BRCT domains were often reported to increase cancer predisposition (28). Moreover, the mutation landscape of BRCA1 seems to be unique in our cohort as those reported in the US (29), Greece (22), India (23) and China (30) did not concentrate in any protein domains. This conclusion, however, needs to be corroborated with a larger number of BRCA1 mutations in future studies.…”

Section: Discussionmentioning

confidence: 63%

Pathogenic Variant Profile of Hereditary Cancer Syndromes in a Vietnamese Cohort

et al. 2022

View full text Add to dashboard Cite

BackgroundHereditary cancer syndromes (HCS) are responsible for 5-10% of cancer cases. Genetic testing to identify pathogenic variants associated with cancer predisposition has not been routinely available in Vietnam. Consequently, the prevalence and genetic landscape of HCS remain unknown.Methods1165 Vietnamese individuals enrolled in genetic testing at our laboratory in 2020. We performed analysis of germline mutations in 17 high- and moderate- penetrance genes associated with HCS by next generation sequencing.ResultsA total of 41 pathogenic variants in 11 genes were detected in 3.2% individuals. The carrier frequency was 4.2% in people with family or personal history of cancer and 2.6% in those without history. The percentage of mutation carriers for hereditary colorectal cancer syndromes was 1.3% and for hereditary breast and ovarian cancer syndrome was 1.6%. BRCA1 and BRCA2 mutations were the most prevalent with the positive rate of 1.3% in the general cohort and 5.1% in breast or ovarian cancer patients. Most of BRCA1 mutations located at the BRCA C-terminus domains and the top recurrent mutation was NM_007294.3:c.5251C>T (p.Arg1751Ter). One novel variant NM_000038.6(APC):c.6665C>A (p.Pro2222His) was found in a breast cancer patient with a strong family history of cancer. A case study of hereditary cancer syndrome was illustrated to highlight the importance of genetic testing.ConclusionThis is the first largest analysis of carrier frequency and mutation spectrum of HCS in Vietnam. The findings demonstrate the clinical significance of multigene panel testing to identify carriers and their at-risk relatives for better cancer surveillance and management strategies.

show abstract

“…We validated 144 patient samples and identi ed prominent gene variants having clinical signi cance. Interestingly, few patients were negative for panel genes and diagnosed with HBOC [14]. This observation led us to investigate novel mutation/s in the whole exonic region which may have role in these cancers.…”

Section: Discussionmentioning

confidence: 99%

“…In that, we identi ed a set of pathogenic variants, VUS and novel variants which readily associated with HBOC risk. Further, we suggested that the mutational pro les of Indian HBOC patients are different from other population suggesting clinical guidelines and genedisease relations reported globally may partly support clinical management of HBOC in Indian population [14]. Interestingly, we noticed few patients which were negative for the multi-gene panel but having breast and/or ovarian cancer and selected 30 patients for the study.…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have reported that the deleterious mutations in non-BRCA genes leading to HBOC conditions [13]. In our previous study, we have designed the next generation sequencing (NGS) based multigene panel to detect the mutations in 18 14 high to moderate risk genes including BRCA and non-BRCA genes for west Indian population [14]. In that, we identi ed a set of pathogenic variants, VUS and novel variants which readily associated with HBOC risk.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of novel exonic variants responsible for hereditary breast and ovarian cancer in West Indian population

Waghela¹,

Pandit²,

Puvar³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Background Breast and ovarian cancers are the most common cancer types in females in India which pertain to higher mortality and morbidity due to late diagnosis and poor prognosis. Early diagnosis for better prognosis improve the patient’s treatment and survival. The next-generation sequencing (NGS)-based screening has accelerated molecular diagnosis of various cancers. Methods We performed whole exome sequencing (WES) of 30 patients who had a first or second degree relative with breast or ovarian cancer. Further, all these patients are tested negative for BRCA1/2 or other high and moderate risk genes reported for HBOC. WES data from 30 patients were analyzed and variants were called using bcftools. Functional annotation of variants and variant prioritization was performed by Exomiser. The clinical significance of variants was determined by Varsome tool. The functional analysis of genes was determined by STRING analysis and disease association was determined by open target tool. Results We examined the variants based on the prevalence of variants among 30 patients i.e. frequency and disease association determined by the phenotype score of exomiser. From both the approaches, we found novel variants and novel gene candidates associated with HBOC conditions. The variants in HYDIN, AVIL, IWS1, PLA2G6, PRDM4, ST3GAL2, and ZNF717 were predicted highly oncogenic. Moreover, we also found 59 genes having higher phenotype score (phenotype score >0.75) and which are associated with various biological processes such as DNA integrity maintenance, transcriptional regulation, cell cycle and apoptosis. Conclusion The gene variants associated with HBOC condition in West Indian cohort have been revisited. Our findings provide novel as well as highly prevalent variants in the population which could be further studied in detail for their use in early diagnosis and better prognosis of HBOC patients.

show abstract

Mutational Landscape for Indian Hereditary Breast and Ovarian Cancer Cohort Suggests Need for Identifying Population Specific Genes and Biomarkers for Screening

Cited by 12 publications

References 24 publications

Analysis of pathogenic variants in BRCA1 and BRCA2 genes using next-generation sequencing in women with triple negative breast cancer from South India

Analysis of pathogenic variants in BRCA1 and BRCA2 genes using next-generation sequencing in women with triple negative breast cancer from South India

Pathogenic Variant Profile of Hereditary Cancer Syndromes in a Vietnamese Cohort

Identification of novel exonic variants responsible for hereditary breast and ovarian cancer in West Indian population

Contact Info

Product

Resources

About