Intratumor heterogeneity of<i>HMCN1</i>mutant alleles associated with poor prognosis in patients with breast cancer

Kikutake, Chie; Yoshihara, Minako; Sato, Tetsuya; Saito, Daisuke; Suyama, Mikita

doi:10.18632/oncotarget.26071

Cited by 22 publications

(16 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the core matrisome, the most frequently mutated gene across cancer types is HMCN1 , which encodes the glycoprotein hemicentin-1, also known as fibulin-6 ( FBN6 ) and a member of the fibulin protein family and component of basement membranes [ 53 ] ( Figure 6 B). While the importance of HMCN1 in cancer progression remains unclear, our data suggest a wider contribution to oncological processes than previously reported [ 54 , 55 ]. Of note, our survey did not find any correlation between the mutational burden in HMCN and cancer patient survival.…”

Section: Resultsmentioning

confidence: 43%

Pan-Cancer Analysis of the Genomic Alterations and Mutations of the Matrisome

Izzi

Davis

Naba

2020

Cancers

View full text Add to dashboard Cite

The extracellular matrix (ECM) is a master regulator of all cellular functions and a major component of the tumor microenvironment. We previously defined the “matrisome” as the ensemble of genes encoding ECM proteins and proteins modulating ECM structure or function. While compositional and biomechanical changes in the ECM regulate cancer progression, no study has investigated the genomic alterations of matrisome genes in cancers and their consequences. Here, mining The Cancer Genome Atlas (TCGA) data, we found that copy number alterations and mutations are frequent in matrisome genes, even more so than in the rest of the genome. We also found that these alterations are predicted to significantly impact gene expression and protein function. Moreover, we identified matrisome genes whose mutational burden is an independent predictor of survival. We propose that studying genomic alterations of matrisome genes will further our understanding of the roles of this compartment in cancer progression and will lead to the development of innovative therapeutic strategies targeting the ECM.

show abstract

Section: Resultsmentioning

confidence: 43%

Pan-Cancer Analysis of the Genomic Alterations and Mutations of the Matrisome

Izzi

Davis

Naba

2020

Cancers

View full text Add to dashboard Cite

show abstract

“…Breast cancer is heterogeneous in nature, and a higher degree of heterogeneity is associated with poor prognosis (18,19). Intratumoral heterogeneity has been assessed noninvasively with breast MRI.…”

mentioning

confidence: 99%

Kinetic Heterogeneity of Breast Cancer Determined Using Computer-aided Diagnosis of Preoperative MRI Scans: Relationship to Distant Metastasis-Free Survival

Kim¹,

Hwangbo²,

Suh³

et al. 2020

Radiology

View full text Add to dashboard Cite

B reast MRI has been commonly used for cancer staging in women with newly diagnosed breast cancer, although controversy remains regarding its generalized use (1,2). In this preoperative setting, breast MRI has been reported to depict additional occult cancer in 10%-30% of ipsilateral breasts (3-5) and in 3%-5% of contralateral breasts in women with breast cancer (3,6,7). Furthermore, preoperative MRI features have been suggested as prognostic imaging markers that can be used to predict outcomes (8)(9)(10)(11)(12). Research is ongoing to identify reliable MRI biomarkers that can guide clinicians in decision making and potentially enable personalized treatment for breast cancer.Breast dynamic contrast material-enhanced (DCE) MRI depicts detailed morphologic features of breast tumors and reveals enhancement kinetics, which may reflect angiogenesis. Commercially available computer-aided diagnosis (CAD) systems provide clinicians with quantitative kinetic information regarding breast tumors on a pixel-by-pixel basis. These CAD systems have been shown to increase the specificity of DCE MRI diagnoses compared with assessments by radiologists through the exclusion of lesions with low threshold enhancement; moreover, they can reduce interpretation time by performing automatic analyses (13)(14)(15). Recent studies have suggested that survival outcomes and CAD-measured kinetic features of breast cancer as observed at preoperative MRI are associated. Kim et al showed that higher values of peak enhancement and washout component were associated with worse disease-free survival (10). Nam et al also found a relationship between higher peak enhancement and poor diseasefree survival (11). However, to our knowledge, there have been no studies of the associations between CAD-extracted kinetic features and distant metastasis outcomes in women with breast cancer. Because angiogenesis plays an important role in tumor growth, tumor progression, and metastasis (16,17), there is a potential for tumor enhancement kinetics to be associated with distant metastasis outcomes.

show abstract

“…Of the 61 genes, several candidates (such as GABRB3, SYNE1, RP13-580B18.4, HMCN1 and SLITRK5) were related to the development of EC. Specifically, GABRB3 is an inhibitory gene of head and neck cancer [ 21 ]; SYNE1 gene hypermethylation can be used as biomarkers in colorectal [ 22 ]; SYNE1 polymorphisms are associated with the risk of developing invasive epithelial ovarian cancer [ 23 ]; intratumoral heterogeneity of HMCN1 mutant alleles is associated with poor prognosis of breast cancer patients [ 24 ]; the combination of SLITRK5 and TP53 is associated with the clinical outcome of gastric cancer patients [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

Integrative analysis of genomic, epigenomic and transcriptomic data identified molecular subtypes of esophageal carcinoma

Chen

Chong

et al. 2021

Aging

View full text Add to dashboard Cite

Esophageal cancer (EC) involves many genomic, epigenetic and transcriptomic disorders, which play key roles in the heterogeneous progression of cancer. However, the study of EC with multi-omics has not been conducted. This study identified a high consistency between DNA copy number variations and abnormal methylations in EC by analyzing genomics, epigenetics and transcriptomics data and investigating mutual correlations of DNA copy number variation, methylation and gene expressions, and stratified copy number variation genes (CNV-Gs) and methylation genes (MET-Gs). The methylation, CNVs and expression profiles of CNV-Gs and MET-Gs were analyzed by consistent clustering using iCluster integration, here, we determined three subtypes (iC1, iC2, iC3) with different molecular traits, prognostic characteristics and tumor immune microenvironment features. We also identified 4 prognostic genes (CLDN3, FAM221A, GDF15 and YBX2) differentially expressed in the three subtypes, and could therefore be used as representative biomarkers for the three subtypes of EC. In conclusion, by performing comprehensive analysis on genomic, epigenetic and transcriptomic regulations, the current study provided new insights into the multilayer molecular and pathological traits of EC, and contributed to the precision medication for EC patients.

show abstract

Intratumor heterogeneity ofHMCN1mutant alleles associated with poor prognosis in patients with breast cancer

Cited by 22 publications

References 55 publications

Pan-Cancer Analysis of the Genomic Alterations and Mutations of the Matrisome

Pan-Cancer Analysis of the Genomic Alterations and Mutations of the Matrisome

Kinetic Heterogeneity of Breast Cancer Determined Using Computer-aided Diagnosis of Preoperative MRI Scans: Relationship to Distant Metastasis-Free Survival

Integrative analysis of genomic, epigenomic and transcriptomic data identified molecular subtypes of esophageal carcinoma

Contact Info

Product

Resources

About