PIK3CA and TP53 Gene Mutations in Human Breast Cancer Tumors Frequently Detected by Ion Torrent DNA Sequencing

<div><p>Breast cancer is the most common malignancy and the leading cause of cancer deaths in women worldwide. While specific genetic mutations have been linked to 5–10% of breast cancer cases, other environmental and epigenetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive breast cancer molecular profile is needed to develop more effective target therapies. Until recently, identifying genetic cancer mutations via personalized DNA sequencing was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 105 human breast cancer samples. The sequencing analysis revealed missense mutations in PIK3CA, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.</p></div

Frequent Mutations in EGFR, KRAS and TP53 Genes in Human Lung Cancer Tumors Detected by Ion Torrent DNA Sequencing

<div><p>Lung cancer is the most common malignancy and the leading cause of cancer deaths worldwide. While smoking is by far the leading cause of lung cancer, other environmental and genetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive lung cancer molecular profile is essential for developing more effective, tailored therapies. Until recently, personalized DNA sequencing to identify genetic mutations in cancer was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 76 human lung cancer samples. The sequencing analysis revealed missense mutations in KRAS, EGFR, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.</p></div

Genetic Mutation Analysis of Human Gastric Adenocarcinomas Using Ion Torrent Sequencing Platform

<div><p>Gastric cancer is the one of the major causes of cancer-related death, especially in Asia. Gastric adenocarcinoma, the most common type of gastric cancer, is heterogeneous and its incidence and cause varies widely with geographical regions, gender, ethnicity, and diet. Since unique mutations have been observed in individual human cancer samples, identification and characterization of the molecular alterations underlying individual gastric adenocarcinomas is a critical step for developing more effective, personalized therapies. Until recently, identifying genetic mutations on an individual basis by DNA sequencing remained a daunting task. Recent advances in new next-generation DNA sequencing technologies, such as the semiconductor-based Ion Torrent sequencing platform, makes DNA sequencing cheaper, faster, and more reliable. In this study, we aim to identify genetic mutations in the genes which are targeted by drugs in clinical use or are under development in individual human gastric adenocarcinoma samples using Ion Torrent sequencing. We sequenced 737 loci from 45 cancer-related genes in 238 human gastric adenocarcinoma samples using the Ion Torrent Ampliseq Cancer Panel. The sequencing analysis revealed a high occurrence of mutations along the TP53 locus (9.7%) in our sample set. Thus, this study indicates the utility of a cost and time efficient tool such as Ion Torrent sequencing to screen cancer mutations for the development of personalized cancer therapy.</p></div

Missense mutation frequencies (including coding silent/deletion/insertion) of 45 genes (737 loci) at different ages in 105 female breast cancer patients.

<p>Missense mutation frequencies (including coding silent/deletion/insertion) of 45 genes (737 loci) at different ages in 105 female breast cancer patients.</p

Missense mutation distribution in the exons and functional domains of PIK3CA.

<p>A. Frequencies of detected mutations in different exons. B. Mutation distribution in exons. C. Mutation distribution in functional domains. D. PIK3CA mutation distribution in correlation with the hormone receptor status in pre- and post-menopausal women.</p

Single and multiple mutations in 105 human breast cancers.

<p>Single and multiple mutations in 105 human breast cancers.</p

Patient info for 105 female breast cancer samples.

<p>Patient info for 105 female breast cancer samples.</p

Single and multiple missense mutations (including coding silent/deletion/insertion) in genes of 76 human lung cancer samples.

<p>Single and multiple missense mutations (including coding silent/deletion/insertion) in genes of 76 human lung cancer samples.</p

Sequence read distribution across 189 amplicons generated from 238 FFPE specimens, normalized to 300,000 reads per sample.

<p>A. Distribution of average coverage of each amplicon. Data are shown as mean ± SD. B. Number of amplicons with a given read depth, sorted in bins of 100 reads. Blue bars represent number of target amplicons within read depth, red line presents % of target amplicons ≥ read depth.</p