Detection of high frequency of mutations in a breast and/or ovarian cancer cohort: implications of embracing a multi-gene panel in molecular diagnosis in India

Mannan, Ashraf U.; Singh, Jaya; Lakshmikeshava, Ravikiran; Thota, Nishita; Singh, Shashikant; Sowmya, T S; Mishra, Avshesh; Sinha, Aditi; Deshwal, Shivani; Soni, Megha Rani; Chandrasekar, Anbukayalvizhi; Ramesh, Bhargavi; Ramamurthy, Bharat; Padhi, Shila; Manek, Payal; Ramalingam, Ravi; Kapoor, Suman; Ghosh, Mithua; Sankaran, Satish; Ghosh, Arunabha; Veeramachaneni, Vamsi; Ramamoorthy, Preveen; Hariharan, Ramesh; Subramanian, Kalyanasundaram

doi:10.1038/jhg.2016.4

Cited by 68 publications

(77 citation statements)

References 39 publications

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“…26 The same mutation was reported in three patients by Mannan et al 19 suggesting that there may be a common ancestry or they migrated from the same place.…”

Section: Discussionmentioning

confidence: 65%

“…18 A recent paper from a company offering sequencing in India showed that occurrence of BRCA mutations in their cases was 36.2%, but this high percentage may be due to the reason that the cases sent for BRCA1 and 2 analysis to the company were mostly of familial type, unlike this study where all cases presenting with BC were used for percentage analysis. 19 Founder mutations are specific sequence variations which appear repeatedly in ethnically defined groups because of shared common ancestry. This effect explains the high frequencies of disease-associated mutations in specific human populations.…”

Section: Discussionmentioning

confidence: 99%

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Pedigree and BRCA gene analysis in breast cancer patients to identify hereditary breast and ovarian cancer syndrome to prevent morbidity and mortality of disease in Indian population

et al. 2017

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Global burden of breast cancer is expected to increase to >2 million new cases every year by 2030 and 10% of these are likely to have hereditary breast and ovarian cancer syndrome. Identifying these individuals by pedigree and BRCA1/2 mutation analyses will enable us to offer targeted mutation testing and appropriate counseling. This study from a tertiary care hospital showed that of the 127 breast cancer patients on treatment during 2014-2015, 24 of them fulfilled the criteria of hereditary breast and ovarian cancer syndrome after detailed verbal autopsy and pedigree analysis, and BRCA1 and 2 next-generation sequencing done after pre-test counseling revealed mutations in 13 cases (54%), these included 9 BRCA1 mutations (69%) and 4 BRCA2 mutation (31%). Subsequent post-test counseling recommended targeted mutation analysis for 64 high-risk members in these 13 families with pathogenic mutations, which will help in surveillance for early detection, appropriate management, and prevention of the disease by decreasing the burden to both family and nation. Results from this preliminary study highlight the importance of genetic counseling, pedigree analysis, and genetic testing. It can be recommended that all oncology units should have a genetic counseling service for providing appropriate support to oncologists, patients, and families to prevent unnecessary testing; however, breast cancer screening program is incomplete without evaluating for hereditary breast and ovarian cancer syndrome.

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“…26 The same mutation was reported in three patients by Mannan et al 19 suggesting that there may be a common ancestry or they migrated from the same place.…”

Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Pedigree and BRCA gene analysis in breast cancer patients to identify hereditary breast and ovarian cancer syndrome to prevent morbidity and mortality of disease in Indian population

et al. 2017

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“…The GG allele was the most frequent similar to European Caucasian population [29]. A characteristic insertion (T>TA) in exon 18 was also found in most of patients (homozygous TA/TA in patients IDs 1,2,4,7,8,9,10,11,13,14,15,16,17,22,23 and 24), (heterozygous T>TA, rs3830355, IVS18-50insA in patients IDs 3, 5,6, 12 and 18). Both PDGFRA exon 18 mutation and exon 12 mutation were related more to gastric and intestinal GIST (gastrointestinal tumors) more than to colonic [30].…”

Section: Missense Splicing and Indels Mutationsmentioning

confidence: 93%

“…Only, NRAS, RET and GNA11 showed coverage less than 95% (≤ 20 reads). For library preparation, Trusight panel DNA library preparation protocol (Illumina) was used [13].…”

Section: Trusight Tumor 15 Panel Illumina Crc Panelmentioning

confidence: 99%

Genetic Variations of Selected Genes Using Target Deep Sequencing in Colorectal Cancer Patients

Farghal¹,

Saied²,

Ghaith³

et al. 2017

J Cancer Sci Ther

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Background: Colorectal carcinoma (CRC) is a burden problem in a developing country like Egypt since patients are usually admitted in late stage with bad prognosis and short overall survival. Because of genetic predisposition of CRC and introduction of advanced molecular techniques, efforts are directed to screen for potential pathogenic or disease-causing variants in CRC patients Methods: DNA was isolated from formalin fixed paraffin embedded tissue sections collected from 24 CRC confirmed diagnosed patients. TruSight CRC panel (Illumina) was used for detection of different variants in 15 genes. The generated reads were obtained from Illumina Miseq were clustered into single nucleotide polymorphism (SNPs) and small insertions/deletions (Indels). Further pathogenic variants with somatic and germline mutations were identified according to the recommended criteria. Some CRC patients were subjected to anti-EGFR target therapy.Results: Most of the variants were detected in TP53 gene 140 variants (65%); 105 short deletions none of them was pathogenic, 29 missense mutations and 6 SNPs at splicing sites. Next, ERBB2 has got 17 variants (8.8%) (missense and splicing), 8 of them were damaging disease causing variants. Besides, 16 pathogenic variants were identified in 12 patients (6 in TP53 and 7 in KRAS). Some pathogenic variants were not reported before in CRC e.g. TP53 C>A, rs121912654, Val157Phe. Additionally, patients carried different KRAS wild mutations showed variable response to anti-EGFR target therapy. Conclusion:The most affected pathway in CRC was TP53 pathway followed by ERBB2, NRAS, KRAS and PIK3CA genes. Variable response to target therapy suggested dependence on the type of pathogenic variant identified, also a possible role of ERBB2 which had a significant variant frequency.NRAS. The prevalence rate of TP53 mutation in Arab population is 52.5% compared to 47.5% in matched Western population [7]. TP53 mutations have roles in determining progression, invasiveness and also metastasis of CRC. So, CRC patients with mutant TP53 have more progressive phenotype and poorer survival than those with TP53 wild type [8]. The phosphatidylinositol 3-kinase/Akt/mammalian target of

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“…Genomic DNA was used for the library preparation for NGS as previously described [Mannan et al, 2016] and sequenced on the NextSeq platform (Illumina) according to the manufacturer's instructions. Variations were identified using the STRAND ® NGS software and imported into StrandOmics TM , a proprietary clinical genomics interpretation and reporting platform.…”

Section: Methodsmentioning

confidence: 99%

1q42.12q42.2 Deletion in a Child with Midline Defects and Hypoplasia of the Corpus Callosum

et al. 2019

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Chromosome 1q42.12q42.2 deletions are documented as “disease causing” and show overlapping phenotypes depending on the genes involved in the deletion. In this report, we detected a 5.8-Mb deletion encompassing the chromosome 1q42.12q42.2 region in a 4-year-old boy with hypoplastic corpus callosum, epilepsy, developmental delay, microcephaly, cataract, cleft palate, and skeletal changes. The deletion was de novo. Genotype-phenotype correlations suggest that the major features of 1q42.12q42.2 microdeletion were attributed to the genes with a high probability of loss-of-function intolerance score in this deletion, namely LBR, ENAH, ACBD3, LIN9, ITPKB, CDC42BPA, ARF1, TAF5L, GALNT2, SPRTN, and EGLN1 along with GNPAT.

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Detection of high frequency of mutations in a breast and/or ovarian cancer cohort: implications of embracing a multi-gene panel in molecular diagnosis in India

Cited by 68 publications

References 39 publications

Pedigree and BRCA gene analysis in breast cancer patients to identify hereditary breast and ovarian cancer syndrome to prevent morbidity and mortality of disease in Indian population

Pedigree and BRCA gene analysis in breast cancer patients to identify hereditary breast and ovarian cancer syndrome to prevent morbidity and mortality of disease in Indian population

Genetic Variations of Selected Genes Using Target Deep Sequencing in Colorectal Cancer Patients

1q42.12q42.2 Deletion in a Child with Midline Defects and Hypoplasia of the Corpus Callosum

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