Dataset Information

Whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer.

ABSTRACT: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Although it is a rare subtype, IBC is responsible for roughly 10% of breast cancer deaths. In order to obtain a better understanding of the genomic landscape and intratumor heterogeneity (ITH) in IBC, we conducted whole-exome sequencing of 16 tissue samples (12 tumor and four normal samples) from six hormone-receptor-positive IBC patients, analyzed somatic mutations and copy number aberrations, and inferred subclonal structures to demonstrate ITH. Our results showed that KMT2C was the most frequently mutated gene (42%, 5/12 samples), followed by HECTD1, LAMA3, FLG2, UGT2B4, STK33, BRCA2, ACP4, PIK3CA, and DNAH8 (all nine genes tied at 33% frequency, 4/12 samples). Our data indicated that PTEN and FBXW7 mutations may be considered driver gene mutations for IBC. We identified various subclonal structures and different levels of ITH between IBC patients, and mutations in the genes EIF4G3, IL12RB2, and PDE4B may potentially generate ITH in IBC.

SUBMITTER: Luo R

PROVIDER: S-EPMC8169683 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer.

Luo Rui R Chong Weelic W Wei Qiang Q Zhang Zhenchao Z Wang Chun C Ye Zhong Z Abu-Khalaf Maysa M MM Silver Daniel P DP Stapp Robert T RT Jiang Wei W Myers Ronald E RE Li Bingshan B Cristofanilli Massimo M Yang Hushan H

NPJ breast cancer 20210601 1

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Although it is a rare subtype, IBC is responsible for roughly 10% of breast cancer deaths. In order to obtain a better understanding of the genomic landscape and intratumor heterogeneity (ITH) in IBC, we conducted whole-exome sequencing of 16 tissue samples (12 tumor and four normal samples) from six hormone-receptor-positive IBC patients, analyzed somatic mutations and copy number aberrations, and inferred subclonal ...[more]

PMID: 34075047

Similar Datasets

Project description:Clear cell renal cell carcinoma (ccRCC) is among the most aggressive histologic subtypes of kidney cancer, representing about 3% of all human cancers. Patients at stage IV have nearly 60% of mortality in 2-3 years after diagnosis. To date, most ccRCC studies have used DNA microarrays and targeted sequencing of a small set of well-established, commonly altered genes. An exception is the large multi-omics study of The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC), which identified new ccRCC genes based on whole exome-sequencing (WES) data, and molecular prognostic signatures based on transcriptomics, epigenetics and proteomics data. Applying WES to simultaneously interrogate virtually all exons in the human genome for somatic variation, here we analyzed the burden of coding somatic mutations in metastatic ccRCC primary tumors, and its association with patient mortality from cancer, in patients who received VEGF receptor-targeting drugs as the first-line therapy. To this end, we sequenced the exomes of ten tumor-normal pairs of ccRCC patient tissues from primary biopsies at >100× mean depth and called somatic coding variation. Mutation burden analysis prioritized 138 genes linked to patient mortality. A gene set enrichment analysis evidenced strong statistical support for the abundance of genes involved in the development of kidney cancer (p = 2.31 × 10-9) and carcinoma (p = 1.22 × 10-5), with 49 genes having direct links with kidney cancer according to the published records. Two of these genes, SIPA1L2 and EIF3A, demonstrated independent associations with mortality in TCGA-KIRC project data. Besides, three mutational signatures were found to be operative in the tumor exomes, one of which (COSMIC signature 12) has not been previously reported in ccRCC. Selection analysis yielded no detectable evidence of overall positive or negative selection, with the exome-wide number of nonsynonymous substitutions per synonymous site reflecting largely neutral tumor evolution. Despite the limited sample size, our results provide evidence for candidate genes where somatic mutation burden is tentatively associated with patient mortality in metastatic ccRCC, offering new potential pharmacological targets and a basis for further validation studies.

Dataset Information

Whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer.

Publications

Whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets