scholarly journals Epithelial-Cadherin Expression Is Associated With Better Recurrence-Free and Overall Survival in Invasive Lobular Breast Cancer in Mexican Women

2021 ◽  
Vol 12 (6) ◽  
pp. 214-224
Author(s):  
Ricardo Fernandez-Ferreira ◽  
Rita Dorantes-Heredia ◽  
Daniel Motola-Kuba ◽  
Jose-Manuel Ruiz-Morales ◽  
Gabriela Alvarado-Luna ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Mexican Women ◽  
Lobular Breast Cancer ◽  
Epithelial Cadherin ◽  
Invasive Lobular Breast Cancer

scholarly journals Association of variably methylated tumour DNA regions with overall survival for invasive lobular breast cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Medha Suman ◽  
Pierre-Antoine Dugué ◽  
Ee Ming Wong ◽  
JiHoon Eric Joo ◽  
John L. Hopper ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Dna Methylation ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Lobular Breast Cancer ◽  
Genome Wide ◽  
Invasive Lobular Breast Cancer

Abstract Background Tumour DNA methylation profiling has shown potential to refine disease subtyping and improve the diagnosis and prognosis prediction of breast cancer. However, limited data exist regarding invasive lobular breast cancer (ILBC). Here, we investigated the genome-wide variability of DNA methylation levels across ILBC tumours and assessed the association between methylation levels at the variably methylated regions and overall survival in women with ILBC. Methods Tumour-enriched DNA was prepared by macrodissecting formalin-fixed paraffin embedded (FFPE) tumour tissue from 130 ILBCs diagnosed in the participants of the Melbourne Collaborative Cohort Study (MCCS). Genome-wide tumour DNA methylation was measured using the HumanMethylation 450K (HM450K) BeadChip array. Variably methylated regions (VMRs) were identified using the DMRcate package in R. Cox proportional hazards regression models were used to assess the association between methylation levels at the ten most significant VMRs and overall survival. Gene set enrichment analyses were undertaken using the web-based tool Metaspace. Replication of the VMR and survival analysis findings was examined using data retrieved from The Cancer Genome Atlas (TCGA) for 168 ILBC cases. We also examined the correlation between methylation and gene expression for the ten VMRs of interest using TCGA data. Results We identified 2771 VMRs (P < 10−8) in ILBC tumours. The ten most variably methylated clusters were predominantly located in the promoter region of the genes: ISM1, APC, TMEM101, ASCL2, NKX6, HIST3H2A/HIST3H2BB, HCG4P3, HES5, CELF2 and EFCAB4B. Higher methylation level at several of these VMRs showed an association with reduced overall survival in the MCCS. In TCGA, all associations were in the same direction, however stronger than in the MCCS. The pooled analysis of the MCCS and TCGA data showed that methylation at four of the ten genes was associated with reduced overall survival, independently of age and tumour stage; APC: Hazard Ratio (95% Confidence interval) per one-unit M-value increase: 1.18 (1.02–1.36), TMEM101: 1.23 (1.02–1.48), HCG4P3: 1.37 (1.05–1.79) and CELF2: 1.21 (1.02–1.43). A negative correlation was observed between methylation and gene expression for CELF2 (R = − 0.25, P = 0.001), but not for TMEM101 and APC. Conclusions Our study identified regions showing greatest variability across the ILBC tumour genome and found methylation at several genes to potentially serve as a biomarker of survival for women with ILBC.

Genomic Characterization of Primary Invasive Lobular Breast Cancer

2016 ◽  
Vol 34 (16) ◽  
pp. 1872-1881 ◽  
Author(s):  
Christine Desmedt ◽  
Gabriele Zoppoli ◽  
Gunes Gundem ◽  
Giancarlo Pruneri ◽  
Denis Larsimont ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Copy Number ◽  
Clinical Investigation ◽  
Endocrine Treatment ◽  
Cancer Genes ◽  
Lobular Breast Cancer ◽  
Primary Tumors ◽  
Histologic Subtype ◽  
Increased Risk ◽  
Invasive Lobular Breast Cancer

Purpose Invasive lobular breast cancer (ILBC) is the second most common histologic subtype after invasive ductal breast cancer (IDBC). Despite clinical and pathologic differences, ILBC is still treated as IDBC. We aimed to identify genomic alterations in ILBC with potential clinical implications. Methods From an initial 630 ILBC primary tumors, we interrogated oncogenic substitutions and insertions and deletions of 360 cancer genes and genome-wide copy number aberrations in 413 and 170 ILBC samples, respectively, and correlated those findings with clinicopathologic and outcome features. Results Besides the high mutation frequency of CDH1 in 65% of tumors, alterations in one of the three key genes of the phosphatidylinositol 3-kinase pathway, PIK3CA, PTEN, and AKT1, were present in more than one-half of the cases. HER2 and HER3 were mutated in 5.1% and 3.6% of the tumors, with most of these mutations having a proven role in activating the human epidermal growth factor receptor/ERBB pathway. Mutations in FOXA1 and ESR1 copy number gains were detected in 9% and 25% of the samples. All these alterations were more frequent in ILBC than in IDBC. The histologic diversity of ILBC was associated with specific alterations, such as enrichment for HER2 mutations in the mixed, nonclassic, and ESR1 gains in the solid subtype. Survival analyses revealed that chromosome 1q and 11p gains showed independent prognostic value in ILBC and that HER2 and AKT1 mutations were associated with increased risk of early relapse. Conclusion This study demonstrates that we can now begin to individualize the treatment of ILBC, with HER2, HER3, and AKT1 mutations representing high-prevalence therapeutic targets and FOXA1 mutations and ESR1 gains deserving urgent dedicated clinical investigation, especially in the context of endocrine treatment.

Sign in / Sign up

Export Citation Format

Share Document