Objectives: The advent of next-generation sequencing (NGS) platforms in the realm of clinical molecular diagnostics provides multigene mutational profiling through massively parallel sequencing.

Methods: We analyzed 415 breast carcinoma samples from 354 patients using NGS in known hotspots of 46 commonly known cancer-causing genes.

Results: A total of 281 somatic nonsynonymous mutations were detected in 62.1% of patients. TP53 was most frequently mutated (38.8%), followed by PIK3CA (31.7%), AKT1 (6%), and ATM (3.9%), with other mutations detected at a lower frequency. When stratified into clinically relevant therapeutic groups (estrogen receptor [ER]/progesterone receptor [PR]+ human epidermal growth factor receptor 2 [HER2]-, ER/PR+HER2+, ER/PR-HER2+, ER/PR/HER2-), each group showed distinct mutational profiles. The ER/PR+HER2- tumors (n = 132) showed the highest frequency of PIK3CA mutations (38%), while the triple-negative tumors (n = 64) had a significantly higher number of TP53 mutations (62%). Of the 61 patients tested for both primary and metastatic tumors, concordant results were seen in 47 (77%) patients, while 13 patients showed additional mutations in the metastasis.

Conclusions: Our results indicate that breast cancers may harbor potentially actionable mutations for targeted therapeutics. Therefore, NGS-based mutational profiling can provide useful information that can guide targeted cancer therapy.

Download full-text PDF

Source
http://dx.doi.org/10.1309/AJCPWDEQYCYC92JQDOI Listing

Publication Analysis

Top Keywords

mutational profiling
12
breast carcinoma
8
next-generation sequencing
8
mutations detected
8
mutations
6
patients
5
multigene clinical
4
mutational
4
clinical mutational
4
profiling breast
4

Similar Publications

Clinical utility and predictive value of cerebrospinal fluid cell-free DNA profiling in non-small cell lung cancer patients with leptomeningeal metastasis.

Neoplasia

December 2024

Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan.

Leptomeningeal metastasis (LM) is a challenging complication of non-small cell lung cancer (NSCLC). Cerebrospinal fluid (CSF) cell-free DNA (cfDNA) analysis using next-generation sequencing (NGS) offers insights into resistance mechanisms and potential treatment strategies. We conducted a study from February 2022 to April 2023 involving patients from five hospitals in Taiwan who had recurrent or advanced NSCLC with LM.

View Article and Find Full Text PDF

A predictive language model for SARS-CoV-2 evolution.

Signal Transduct Target Ther

December 2024

School of Basic Medical Science, Tsinghua University, 30 Shuangqing Rd., Haidian District, Beijing, 100084, China.

Modeling and predicting mutations are critical for COVID-19 and similar pandemic preparedness. However, existing predictive models have yet to integrate the regularity and randomness of viral mutations with minimal data requirements. Here, we develop a non-demanding language model utilizing both regularity and randomness to predict candidate SARS-CoV-2 variants and mutations that might prevail.

View Article and Find Full Text PDF

This study delves into the combined effects of seasonal climate variations and MIPS1 gene mutations on the germination rates of soybean cultivars TW-1 and TW75. Through comprehensive metabolomic and transcriptomic analyses, we identified key KEGG pathways significantly affected by these factors, including starch and sucrose metabolism, lipid metabolism, and amino acid biosynthesis. These pathways were notably disrupted during the spring, leading to an imbalance in metabolic reserves critical for seedling development.

View Article and Find Full Text PDF

Hairy cell proliferations represent very different entities. They include hairy cell leukemia in its classic form (HCL), a well-defined entity, but also the variant form of HCL (LT-V ou HCL-V), whose presentation is far from HCL and whose prognosis is poorer. Other hairy cell proliferations include splenic red pulp lymphoma (SDRPL) and splenic marginal zone lymphomas (SMZL) with circulating villous cells.

View Article and Find Full Text PDF

Emerging molecular phenotypes and potential therapeutic targets in esophageal and gastric adenocarcinoma unearthed by whole genome and transcriptome analyses.

Pathol Res Pract

December 2024

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA. Electronic address:

Background: Adenocarcinoma of the esophagus and stomach demands a deeper molecular understanding to advance treatment strategies and improve patient outcomes. Here, we profiled the genome and transcriptome landscape of these cancers, explored molecular characteristics that are undetectable by other sequencing platforms, and analyzed their potential clinical ramifications.

Methods: Our study employed state-of-the-art integrative analyses of whole genome and transcriptome sequencing on 51 matched tumor and germline samples from 46 patients.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!