scholarly journals The Genomic Landscape of Lobular Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1950
Author(s):  
Amy E. McCart Reed ◽  
Samuel Foong ◽  
Jamie R. Kutasovic ◽  
Katia Nones ◽  
Nicola Waddell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Lobular Carcinoma ◽  
The Cancer Genome Atlas ◽  
Whole Genome Sequencing Data ◽  
Breast Cancers ◽  
Sequencing Data ◽  
Tumour Type ◽  
Histologic Subtype ◽  
Genomic Landscape

Invasive lobular carcinoma (ILC) is the second most common breast cancer histologic subtype, accounting for approximately 15% of all breast cancers. It is only recently that its unique biology has been assessed in high resolution. Here, we present a meta-analysis of ILC sequencing datasets, to provide a long-awaited ILC-specific resource, and to confirm the prognostic value and strength of association between a number of clinico-pathology features and genomics in this special tumour type. We consider panel (n = 684), whole exome (n = 215) and whole genome sequencing data (n = 48), and review histology of The Cancer Genome Atlas cases to assign grades and determine whether the ILC is of classic type or a variant, such as pleomorphic, prior to performing statistical analyses. We demonstrate evidence of considerable genomic heterogeneity underlying a broadly homogeneous tumour type (typically grade 2, estrogen receptor (ER)-positive); with genomes exhibiting few somatic mutations or structural alterations, genomes with a hypermutator phenotype, and tumours with highly rearranged genomes. We show that while CDH1 (E-cadherin) and PIK3CA mutations do not significantly impact survival, overall survival is significantly poorer for patients with a higher tumour mutation burden; this is also true for grade 3 tumours, and those carrying a somatic TP53 mutation (and these cases were more likely to be ER-negative). Taken together, we have compiled a meta-dataset of ILC with molecular profiling, and our analyses show that the genomic landscape significantly impacts the tumour’s variable natural history and overall survival of ILC patients.

Neuroendocrine tumours of the breast: a genomic comparison with mucinous breast cancers and neuroendocrine tumours of other anatomic sites

2020 ◽  
pp. jclinpath-2020-207052
Author(s):  
Fresia Pareja ◽  
Mahsa Vahdatinia ◽  
Caterina Marchio ◽  
Simon S K Lee ◽  
Arnaud Da Cruz Paula ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factors ◽  
Neuroendocrine Tumours ◽  
Neuroendocrine Differentiation ◽  
Genetic Alterations ◽  
Breast Cancers ◽  
Sequencing Data ◽  
Histologic Subtype ◽  
Er Positive ◽  
Positive Breast Cancer

AimsBreast neuroendocrine tumours (NETs) constitute a rare histologic subtype of oestrogen receptor (ER)-positive breast cancer, and their definition according to the WHO classification was revised in 2019. Breast NETs display histologic and transcriptomic similarities with mucinous breast carcinomas (MuBCs). Here, we sought to compare the repertoire of genetic alterations in breast NETs with MuBCs and NETs from other anatomic origins.MethodsOn histologic review applying the new WHO criteria, 18 breast tumours with neuroendocrine differentiation were reclassified as breast NETs (n=10) or other breast cancers with neuroendocrine differentiation (n=8). We reanalysed targeted sequencing or whole-exome sequencing data of breast NETs (n=10), MuBCs type A (n=12) and type B (n=11).ResultsBreast NETs and MuBCs were found to be genetically similar, harbouring a lower frequency of PIK3CA mutations, 1q gains and 16q losses than ER-positive/HER2-negative breast cancers. 3/10 breast NETs harboured the hallmark features of ER-positive disease (ie, PIK3CA mutations and concurrent 1q gains/16q losses). Breast NETs showed an enrichment of oncogenic/likely oncogenic mutations affecting transcription factors compared with common forms of ER-positive breast cancer and with pancreatic and pulmonary NETs.ConclusionsBreast NETs are heterogeneous and are characterised by an enrichment of mutations in transcription factors and likely constitute a spectrum of entities histologically and genomically related to MuBCs. While most breast NETs are distinct from ER-positive/HER2-negative IDC-NSTs, a subset of breast NETs appears to be genetically similar to common forms of ER-positive breast cancer, suggesting that some breast cancers may acquire neuroendocrine differentiation later in tumour evolution.

scholarly journals Identification of novel cell glycolysis related gene signature predicting survival in patients with breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Feng Jiang ◽  
Chuyan Wu ◽  
Ming Wang ◽  
Ke Wei ◽  
Jimei Wang
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Single Gene ◽  
Prediction Method ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Cox Models ◽  
Normal Tissues ◽  
Predictive Risk

AbstractOne of the most frequently identified tumors and a contributing cause of death in women is breast cancer (BC). Many biomarkers associated with survival and prognosis were identified in previous studies through database mining. Nevertheless, the predictive capabilities of single-gene biomarkers are not accurate enough. Genetic signatures can be an enhanced prediction method. This research analyzed data from The Cancer Genome Atlas (TCGA) for the detection of a new genetic signature to predict BC prognosis. Profiling of mRNA expression was carried out in samples of patients with TCGA BC (n = 1222). Gene set enrichment research has been undertaken to classify gene sets that vary greatly between BC tissues and normal tissues. Cox models for additive hazards regression were used to classify genes that were strongly linked to overall survival. A subsequent Cox regression multivariate analysis was used to construct a predictive risk parameter model. Kaplan–Meier survival predictions and log-rank validation have been used to verify the value of risk prediction parameters. Seven genes (PGK1, CACNA1H, IL13RA1, SDC1, AK3, NUP43, SDC3) correlated with glycolysis were shown to be strongly linked to overall survival. Depending on the 7-gene-signature, 1222 BC patients were classified into subgroups of high/low-risk. Certain variables have not impaired the prognostic potential of the seven-gene signature. A seven-gene signature correlated with cellular glycolysis was developed to predict the survival of BC patients. The results include insight into cellular glycolysis mechanisms and the detection of patients with poor BC prognosis.

scholarly journals Identification of the angiogenesis related genes for predicting prognosis of patients with gastric cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sheng Zheng ◽  
Zizhen Zhang ◽  
Ning Ding ◽  
Jiawei Sun ◽  
Yifeng Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
High Efficiency ◽  
Cox Regression ◽  
Risk Group ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Lasso Regression ◽  
Sequencing Data ◽  
Cox Regression Analysis

Abstract Introduction Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC). Methods mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis‑associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively. Results Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan–Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusions We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It’s assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.

scholarly journals Heme Biosynthesis mRNA Expression Signature: Towards a Novel Prognostic Biomarker in Patients with Diffusely Infiltrating Gliomas

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 662
Author(s):  
Mario Mischkulnig ◽  
Barbara Kiesel ◽  
Daniela Lötsch ◽  
Thomas Roetzer ◽  
Martin Borkovec ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mrna Expression ◽  
Postoperative Management ◽  
Heme Biosynthesis ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Who Grade ◽  
Expression Signature ◽  
Cancer Genome Atlas ◽  
The Impact

Diffusely infiltrating gliomas are characterized by a variable clinical course, and thus novel prognostic biomarkers are needed. The heme biosynthesis cycle constitutes a fundamental metabolic pathway and might play a crucial role in glioma biology. The aim of this study was thus to investigate the role of the heme biosynthesis mRNA expression signature on prognosis in a large glioma patient cohort. Glioma patients with available sequencing data on heme biosynthesis expression were retrieved from The Cancer Genome Atlas (TCGA). In each patient, the heme biosynthesis mRNA expression signature was calculated and categorized into low, medium, and high expression subgroups. Differences in progression-free and overall survival between these subgroups were investigated including a multivariate analysis correcting for WHO grade, tumor subtype, and patient age and sex. In a total of 693 patients, progression-free and overall survival showed a strictly monotonical decrease with increasing mRNA expression signature subgroups. In detail, median overall survival was 134.2 months in the low, 79.9 months in the intermediate, and 16.5 months in the high mRNA expression signature subgroups, respectively. The impact of mRNA expression signature on progression-free and overall survival was independent of the other analyzed prognostic factors. Our data indicate that the heme biosynthesis mRNA expression signature might serve as an additional novel prognostic marker in patients with diffusely infiltrating gliomas to optimize postoperative management.

scholarly journals O29 Aberrant expression of BMP8A and the BMPRs involves in the progression of breast cancer

2021 ◽  
Vol 108 (Supplement_5) ◽  
Author(s):  
L J Sui ◽  
A Sanders ◽  
W G Jiang ◽  
L Ye
Keyword(s):  
Breast Cancer ◽  
Poor Prognosis ◽  
Gene Array ◽  
Breast Cancers ◽  
Sequencing Data ◽  
Aberrant Expression ◽  
Bmp Receptors ◽  
Significant Difference ◽  
Highly Correlated ◽  
Spearman Test

Abstract Introduction Role of Bone morphogenetic protein 8A (BMP8A) and BMP receptors (BMPRs) in the tumourigenesis and progression of breast cancer remains elusive. Present study aims to investigate the expression of BMP8A and related BMPRs in breast cancer and their clinical implication. Method Expression of BMP8A and BMPRs was analysed using the RNA sequencing data of the TCGA breast cancer cohort. Findings were further validated in a meta gene array dataset (E-MDTA6703, n = 2302). STRING dataset was applied to explore the predicted receptors of BMP8A. Clinical relevance of deregulated BMP8A and BMPRs in breast cancer was assessed using both ANOVA and Kaplan-Meier tests. Correlation with markers of proliferation and invasion was evaluated using Spearman test. Result Analysis of datasets revealed that BMP8A and BMPR1B were highly expressed in breast cancer while ACVRL1, ACVR1, BMPR1A, ACVR1C, TGFBR2, TGFBR3, BMPR2 and ACVR2A were lower-expressed compared with normal controls. Expressions of BMPR1B, BMPR1A, BMPR2, ACVR2A and ACVR2B were highly correlated with BMP8A in the breast cancers. Overall survival in the group with higher BMP8A expression was shorter(median= 122.3 months), P = 0.012 compared with lower-expressed group(median = 215.2 months). No significant difference was observed in BMP8A and BMPRs in tumours according to their staging and lymph node involvement. Positive correlations were found between BMP8A and tumour proliferation, EMT, angiogenic markers. Conclusion BMP8A is increased in breast cancer and correlates with poor prognosis. The highly correlated BMPRs might be involved in the signal transduction of BMP8A to co-regulate BMP responsive genes and cellular functions which is yet to be investigated. Take-home Message BMP8A is increased in breast cancer and correlates with poor prognosis.

scholarly journals Molecular basis of distinct oestrogen responses in endometrial and breast cancer

2019 ◽  
Vol 26 (1) ◽  
pp. 31-46 ◽  
Author(s):  
Eva Baxter ◽  
Karolina Windloch ◽  
Greg Kelly ◽  
Jason S Lee ◽  
Frank Gannon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcriptional Activation ◽  
The Cancer Genome Atlas ◽  
Breast Cancers ◽  
Oestrogen Receptor Alpha ◽  
Limited Success ◽  
Cancer Genome Atlas ◽  
Using Data ◽  
Oestrogen Signalling

Up to 80% of endometrial and breast cancers express oestrogen receptor alpha (ERα). Unlike breast cancer, anti-oestrogen therapy has had limited success in endometrial cancer, raising the possibility that oestrogen has different effects in both cancers. We investigated the role of oestrogen in endometrial and breast cancers using data from The Cancer Genome Atlas (TCGA) in conjunction with cell line studies. Using phosphorylation of ERα (ERα-pSer118) as a marker of transcriptional activation of ERα in TCGA datasets, we found that genes associated with ERα-pSer118 were predominantly unique between tumour types and have distinct regulators. We present data on the alternative and novel roles played by SMAD3, CREB-pSer133 and particularly XBP1 in oestrogen signalling in endometrial and breast cancer.

Metaplastic Breast Cancer: Clinical Features and Outcomes

2005 ◽  
Vol 71 (9) ◽  
pp. 725-730 ◽  
Author(s):  
Glen R. Gibson ◽  
Dajun Qian ◽  
Joseph K. Ku ◽  
Lily L. Lai
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Local Recurrence ◽  
Menopausal Status ◽  
Axillary Node ◽  
Metaplastic Carcinoma ◽  
Metaplastic Breast Cancer ◽  
Histologic Subtype ◽  
Hormone Receptor Positive ◽  
Node Involvement

Metaplastic carcinoma of the breast, a neoplasm with both epithelial and mesenchymal elements, represents less than 1 per cent of all breast cancer. We reviewed the records of all patients diagnosed with localized metaplastic breast cancer from 1991 to 2003 at our institution. We identified 21 patients. Mean primary tumor size was 4.62 cm. Eight patients (38%) had axillary node involvement at presentation. All the tumors were high grade. Only two (10%) of the tumors were hormone receptor positive. Seventeen (81%) of the patients received adjuvant chemotherapy, and 12 (57%) of the patients received radiation. Ten (29%) patients suffered a local recurrence. With a mean follow-up of 46 months, the 5-year disease-free and overall survival was 42 per cent (95% CI: 20% to 65%) and 71 per cent (95% CI: 46% to 96%), respectively. Stage-specific overall survival was 100 per cent, 83 per cent, and 53 per cent for stages I, II, and III, respectively. By multivariate analysis, there was no impact on recurrence or survival with regard to size, age, menopausal status, nodal status, histologic subtype, adjuvant therapy, or extent of surgery. Metaplastic breast cancer is a unique neoplasm that tends to present at an advanced stage and has a propensity for local recurrence. When stratified by stage, however, survival appears similar to that of adenocarcinoma of the breast, and these tumors should be treated as such.

scholarly journals Recurrent hormone-binding domain truncated ESR1 amplifications in primary endometrial cancers suggest their implication in hormone independent growth

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Frederik Holst ◽  
Erling A. Hoivik ◽  
William J. Gibson ◽  
Amaro Taylor-Weiner ◽  
Steven E. Schumacher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Acquired Resistance ◽  
Estrogen Therapy ◽  
Binding Domain ◽  
The Cancer Genome Atlas ◽  
Breast Cancers ◽  
Hormone Binding ◽  
Therapeutic Implications ◽  
Hormone Binding Domain

Abstract The estrogen receptor alpha (ERα) is highly expressed in both endometrial and breast cancers, and represents the most prevalent therapeutic target in breast cancer. However, anti-estrogen therapy has not been shown to be effective in endometrial cancer. Recently it has been shown that hormone-binding domain alterations of ERα in breast cancer contribute to acquired resistance to anti-estrogen therapy. In analyses of genomic data from The Cancer Genome Atlas (TCGA), we observe that endometrial carcinomas manifest recurrent ESR1 gene amplifications that truncate the hormone-binding domain encoding region of ESR1 and are associated with reduced mRNA expression of exons encoding the hormone-binding domain. These findings support a role for hormone-binding alterations of ERα in primary endometrial cancer, with potentially important therapeutic implications.

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