No April fools in clinical genomics

McNeill, Alisdair

doi:10.1038/s41431-022-01084-z

Cited by 3 publications

(2 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The prevalence of BRCA1 and BRCA2 mutations varies in different populations (20,21). Decision making for the test is important for patient-centred medical care and risk-reducing treatments (22,23).…”

Section: Discussionmentioning

confidence: 99%

BRCA1 and BRCA2 gene mutation spectrum and high frequency of BRCA1 185delAG among breast and ovarian cancer patients from Southern India.

Chapla,

John,

Singh

et al. 2023

Preprint

View full text Add to dashboard Cite

In a developing country like India, genomic data sets for even the most clinically relevant genes like BRCA1 and BRCA2 are relatively scarce. There is also a need to identify and screen population specific BRCA hotspot mutations to pave the way for affordable genetic testing strategies in clinical practice. We have carried out an ambispective study to evaluate Next-generations Sequencing (NGS) based approach to identify pathogenic variants in BRCA1 and BRCA2 genes among 772 breast and ovarian cancer patients. The target enrichment was carried out using the in-house designed Multiplex-PCR for BRCA1 and BRCA2, followed by targeted NGS on Ion Torrent Personal Genome Machine. Additionally, allele-specific PCR (ASPCR) based genotyping of BRCA1 c.68_69delAG also known as 185delAG, was carried out in 149 patients. We identified 181 BRCA1 and BRCA2 variants, and based on ACMG 2015 guidelines, these variants were classified as 111 pathogenic or likely pathogenic and 70 VUS (Variant with uncertain significance). The 185delAG was identified as a recurrent mutation in the Southern Indian population accounting for 25.21% of the pathogenic variants. In addition, a family history of cancers of the breast, ovary, pancreas, or prostate (BOPP) was found to be associated with a higher risk of identifying a deleterious BRCA1/2 variant [OR=2.15 (95%CI 1.46-3.2) p≤0.0001]. These results suggest that Multiplex PCR coupled NGS is a sensitive and specific strategy for BRCA testing. However, ASPCR-based genotyping of 185delAG followed by targeted NGS would be cost-effective in South Indian patients.

show abstract

Section: Discussionmentioning

confidence: 99%

BRCA1 and BRCA2 gene mutation spectrum and high frequency of BRCA1 185delAG among breast and ovarian cancer patients from Southern India.

Chapla,

John,

Singh

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…The prevalence of BRCA1 and BRCA2 mutations vary in different populations [20,21]. Decision making for the test is important for patient-centred medical care and risk-reducing treatments [22,23].…”

Section: Discussionmentioning

confidence: 99%

BRCA1 and BRCA2 gene mutation spectrum and a high frequency of BRCA1 185delAG among breast and ovarian cancer patients from Southern India.

John

Singh

Joel

et al. 2022

Preprint

View full text Add to dashboard Cite

Purpose In a developing country like India, genomic data sets for even the most clinically relevant genes like BRCA1 and BRCA2 is rather scarce. Also, there is a need to identify and screen population specific BRCA hotspots to pave a way for affordable genetic testing strategies in clinical practice. Method This is an ambispective study to evaluate an NGS based approach to identify pathogenic variants in BRCA1 and BRCA2 genes among 430 patients with Breast and Ovarian cancers. The target enrichment was carried out using the in-house designed Multiplex-PCR followed by targeted Next-generation sequencing (NGS) for BRCA1 and BRCA2. Also, allele-specific PCR based genotyping of del185AG was carried out in additional 120 patients. Results In this study, we have identified 100 BRCA1 and BRCA2 variants and based on ACMG 2015 guidelines, these variants were classified as 46 pathogenic, 9 likely pathogenic, and 45 VUS. Of these variants, three were novel, two with likely pathogenic, and one variant of uncertain significance (VUS). The 185delAG was identified as a recurrent mutation in the Southern Indian population accounting for 25.45% of the pathogenic variants. In addition, a family history of cancers of the breast, ovary, pancreas, or prostate (BOPP) was found to be associated with a higher risk of identifying a deleterious BRCA1/2 variant [OR 3.2 (95%CI 1.84–5.77) p ≤ 0.001]. Conclusions These results suggest that Multiplex PCR-NGS is a sensitive and specific strategy for BRCA testing. However, ASPCR-based genotyping of BRCA1(NM_007300.4): c.68_69del followed by targeted NGS would be a cost-effective approach in south Indian patients.

show abstract

The BRCA mutation spectrum among breast and ovarian cancers in India: highlighting the need to screen BRCA1 185delAG among South Indians

John,

Singh,

Yadav

et al. 2024

Eur J Hum Genet

View full text Add to dashboard Cite

No April fools in clinical genomics

Cited by 3 publications

References 12 publications

BRCA1 and BRCA2 gene mutation spectrum and high frequency of BRCA1 185delAG among breast and ovarian cancer patients from Southern India.

BRCA1 and BRCA2 gene mutation spectrum and high frequency of BRCA1 185delAG among breast and ovarian cancer patients from Southern India.

BRCA1 and BRCA2 gene mutation spectrum and a high frequency of BRCA1 185delAG among breast and ovarian cancer patients from Southern India.

The BRCA mutation spectrum among breast and ovarian cancers in India: highlighting the need to screen BRCA1 185delAG among South Indians

Contact Info

Product

Resources

About