Low-Frequency Mutational Heterogeneity of Invasive Ductal Carcinoma Subtypes: Information to Direct Precision Oncology

International Journal of Molecular Sciences
Meagan B MyersBarbara L Parsons

Abstract

Information regarding the role of low-frequency hotspot cancer-driver mutations (CDMs) in breast carcinogenesis and therapeutic response is limited. Using the sensitive and quantitative Allele-specific Competitor Blocker PCR (ACB-PCR) approach, mutant fractions (MFs) of six CDMs (PIK3CA H1047R and E545K, KRAS G12D and G12V, HRAS G12D, and BRAF V600E) were quantified in invasive ductal carcinomas (IDCs; including ~20 samples per subtype). Measurable levels (i.e., ≥ 1 × 10-5, the lowest ACB-PCR standard employed) of the PIK3CA H1047R, PIK3CA E545K, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E mutations were observed in 34/81 (42%), 29/81 (36%), 51/81 (63%), 9/81 (11%), 70/81 (86%), and 48/81 (59%) of IDCs, respectively. Correlation analysis using available clinicopathological information revealed that PIK3CA H1047R and BRAF V600E MFs correlate positively with maximum tumor dimension. Analysis of IDC subtypes revealed minor mutant subpopulations of critical genes in the MAP kinase pathway (KRAS, HRAS, and BRAF) were prevalent across IDC subtypes. Few triple-negative breast cancers (TNBCs) had appreciable levels of PIK3CA mutation, suggesting that individuals with TNBC may be less responsive to inhibitors of the PI3K/AKT/mTOR pa...Continue Reading

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Citations

Aug 31, 2019·Environmental and Molecular Mutagenesis·Kelly L HarrisBarbara L Parsons
Sep 18, 2020·Environmental and Molecular Mutagenesis·Kelly L HarrisBarbara L Parsons
May 18, 2020·Clinical Breast Cancer·Nupur Mukherjee, Chinmay Kumar Panda
Mar 7, 2021·International Journal of Molecular Sciences·Przemysław KołodziejAnna Bogucka-Kocka
Apr 7, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Karen L McKimBarbara L Parsons
Aug 11, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Kelly L HarrisBarbara L Parsons

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Methods Mentioned

BETA
array technologies
PCR
transgenic
reverse phase chromatography

Software Mentioned

GraphPad Prism
Quantity One

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