Targeted Resequencing of 30 Genes Improves the Detection of Deleterious Mutations in South Indian Women with Breast and/or Ovarian Cancers

Abstract

Background: We earlier used PCR-dHPLC for mutation analysis of BRCA1 and BRCA2. In this article we report application of targeted resequencing of 30 genes involved in hereditary cancers. Materials and Methods: A total of 91 patient samples were analysed using a panel of 30 genes in the Illumina HiScan SQ system. CLCBio was used for mapping reads to the reference sequences as well as for quality-based variant detection. All the deleterious mutations were then reconfirmed using Sanger sequencing. Kaplan Meier analysis was conducted to assess the effect of deleterious mutations on disease free and overall survival. Results: Seventy four of the 91 samples had been run earlier using the PCR-dHPLC and no deleterious mutations had been detected while 17 samples were tested for the first time. A total of 24 deleterious mutations were detected, 11 in BRCA1, 4 in BRCA2, 5 in p53, one each in RAD50, RAD52, ATM and TP53BP1. Some 19 deleterious mutations were seen in patients who had been tested earlier with PCR-dHPLC [19/74] and 5/17 in the samples tested for the first time, Together with our earlier detected 21 deleterious mutations in BRCA1 and BRCA2, we now had 45 mutations in 44 patients. BRCA1c.68_69delAG;p.Glu23ValfsX16 mutation was the most common, seen in 10/44 patients. Kaplan Meier survival analysis did not show any difference in disease free and overall survival in the patients with and without deleterious mutations. Conclusions: The NGS platform is more sensitive and cost effective in detecting mutations in genes involved in hereditary breast and/or ovarian cancers.

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

“…20,21 Indian studies reported a frequency of this mutation in 0.5%-4.1% BC cases in different states. [22][23][24] This was also reported in two south Indian families by Rajkumar et al 22 in 2015. We also found this mutation in two of our breast cancer patients, who hailed from the coastal region of India (i.e.…”

The frequency of cancer predisposition gene mutations in hereditary breast and ovarian cancer patients in Taiwan: From BRCA1/2 to multi-gene panels

“…We observed that the prevalence of non- BRCA1 /2 genes was 7.5% based on 68 genes, 11.5% based on 49 genes and 8.2% based on all cases in our study ( Table 1 ). By using a 30-gene panel, a study of South Indian women with HBOC found a mutation rate of 9.8% among non- BRCA1/2 genes (9/91) [ 43 ]. Moreover, Wong et al identified 47.8% of pathogenic variants in non- BRCA1/2 genes among 220 HBOC patients in Singapore [ 44 ], and a mutation rate of 6% was observed for non- BRCA1/2 genes based on a 15-gene panel in a Malaysian BC patient study [ 45 ].…”

Current review ofTP53pathogenic germline variants in breast cancer patients outside Li-Fraumeni syndrome

“…While most of the published multigene panel studies tested patients of (mostly) European ancestry, a limited number of studies have analyzed other populations. We therefore compared the frequency of TP53 carriers among cohorts of patients with different ancestries and without previous BRCA1/2 testing (BRCA unknown) for Europeans (Bunnell et al., ; Buys et al., ; Castera et al., ; Couch et al., ; Couch et al., ; Doherty, Bonadies, & Matloff, ; Eliade et al., ; Kapoor et al., ; Kraus et al., ; Moran et al., ; Pinto et al., ; Rummel, Lovejoy, Shriver, & Ellsworth, ; Schroeder et al., ; Shirts et al., ; Susswein et al., ; Tedaldi et al., ; Tung et al., ; Tung et al., ) Asians (Kwong et al., ; Lin et al., ; Ng et al., ; Rajkumar, Meenakumari, Mani, Sridevi, & Sundersingh, ; Wong et al., ; Yang et al., ), and Middle Easterns (Jalkh et al., ; Lolas Hamameh et al., ).…”