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- Title
An Investigation Into The Mutational Spectrum And Sub-Types Of Tnbcs In Indians; A Population With High Proportion Of Tnbcs.
- Authors
Prabhu, Jyothi S.; Rajarajan, Savitha; Hari, P. S.
- Abstract
TNBC is a heterogeneous disease and the subtypes reported by Lehman B et al in 2014 differ in their gene expression profiles, mutational spectrum and the extent of immune infiltrates. Indians have a higher proportion of TNBC (~ 30%) with a greater number of younger women and clinico-epidemiological features that resemble that of the ethnic African American (AA) population (Kakarala M et al 2010). We have earlier reported the use of the BRCA1/ID4 transcript ratio, as a measure of BRCA1 deficiency in TNBCs (Korlimarla A et al 2016). Here we examined the mutational spectrum in a fraction of our TNBC tumors. We sequenced somatic DNA from 25 TNBCs (FFPE Specimens) on Illumina MiSeq V2 150x2, from a non-consecutive retrospective case-series of close to 200 tumors (comprising 30% TNBC) from a regional cancer centre in Southern India. The TruSeqAmplicon - Cancer Panel Kit (Illumina) comprising of 212 DNAspecific amplicons covering hotspots in 48 cancer associated genes was used to construct the libraries. Variant calling was done following ACMG guidelines. Data from our series was compared to TCGA. The most frequently mutated genes were TP53, followed by PIK3CA and KRAS indicating similarity in the biology of the disease compared to that reported in the TCGA set (N=102). At 80%, the frequency of TP53 mutations in our set was comparable with that of Caucasians (70%) and AA (73%). However, we noted a statistically significantly higher proportion of PIK3CA mutations (7/25 =28%) as compared to ~8% in TCGA set (8/102) of which, there were none in AA (0/20), (p=0.003). Curiously enough frequency of KRAS mutations was also high at 24% which has not been earlier reported. Is the mutation profile of Indian TNBCs different from that of the west? A more detailed analysis of this work validated on a cohort with outcomes and survival data is underway. Since very little is known about the mutation landscape of Indian TNBCs, analysis of the mutational spectrum and identification of actionable mutations in TNBCs can help target therapy.
- Subjects
KARST (Slovenia &; Italy : Region); INDIA; ALOPECIA areata; GENE expression profiling; CANCER genes; SPECTRUM analysis; POPULATION; BIOLOGY
- Publication
Journal of Cancer Research & Therapeutics, 2017, Vol 13, pS106
- ISSN
0973-1482
- Publication type
Article