Abstract:
BACKGROUND:Sequence variations in coding and non-coding regions of the genome can affect gene expression and signalling pathways, which in turn may influence disease outcome. METHODS:In this study, we integrated somatic mutations, gene expression and clinical data from 930 breast cancer patients included in the TCGA database. Genes associated with single mutations in molecular breast cancer subtypes were identified by the Mann-Whitney U-test and their prognostic value was evaluated by Kaplan-Meier and Cox regression analyses. Results were confirmed using gene expression profiles from the Metabric data set (n = 1988) and whole-genome sequencing data from the TCGA cohort (n = 117). RESULTS:The overall mutation rate in coding and non-coding regions were significantly higher in ER-negative/HER2-negative tumours (P = 2.8E-03 and P = 2.4E-07, respectively). Recurrent sequence variations were identified in non-coding regulatory regions of several cancer-associated genes, including NBPF1, PIK3CA and TP53. After multivariate regression analysis, gene signatures associated with three coding mutations (CDH1, MAP3K1 and TP53) and two non-coding variants (CRTC3 and STAG2) in cancer-related genes predicted prognosis in ER-positive/HER2-negative tumours. CONCLUSIONS:These findings demonstrate that sequence alterations influence gene expression and oncogenic pathways, possibly affecting the outcome of breast cancer patients. Our data provide potential opportunities to identify non-coding variations with functional and clinical relevance in breast cancer.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Győrffy B,Pongor L,Bottai G,Li X,Budczies J,Szabó A,Hatzis C,Pusztai L,Santarpia Ldoi
10.1038/s41416-018-0030-0subject
Has Abstractpub_date
2018-04-01 00:00:00pages
1107-1114issue
8eissn
0007-0920issn
1532-1827pii
10.1038/s41416-018-0030-0journal_volume
118pub_type
杂志文章abstract::Three biochemical markers of collagen metabolism were measured in 39 osteosarcoma patients. The pretreatment values did not predict outcome, and the markers showed no consistent change upon development of metastases. Both the age of the patients and the multimodality therapy affected the collagen metabolites. These fi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.19
更新日期:1996-01-01 00:00:00
abstract:BACKGROUND:This phase 1 study examined the safety, maximum-tolerated dose (MTD) and antitumour activity of E7449, a novel PARP 1/2 and tankyrase 1/2 inhibitor. METHODS:E7449 was orally administered once daily in 28-day cycles to patients with advanced solid tumours (50-800-mg doses). Archival tumour samples from conse...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-0916-5
更新日期:2020-08-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:British journal of cancer
pub_type: 已发布勘误
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更新日期:2020-08-01 00:00:00
abstract::The cytotoxicity of methotrexate (MTX) on representative human tumour cell lines (two cell lines from head and neck carcinomas, two from breast carcinomas, two from osteosarcomas and one lymphoblastoid cell line) was evaluated to: (1) examine the optimal time interval between MTX and folinic acid (FA) administration; ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1991.70
更新日期:1991-02-01 00:00:00
abstract::A study was conducted on the effects of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on peroxisomal enzyme activities in mouse embryo fibroblasts C3H/10T1/2 C18 cells and chemically transformed C3H/10T1/2 MCA16 cells. TPA is a potent tumour promoter and treatment with this compound of the two cell lines induced peroxis...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1986.17
更新日期:1986-01-01 00:00:00
abstract::The prognostic value of tissue-type plasminogen activator (tPA) measured in samples derived from 865 patients with primary breast cancer using a recently developed enzyme-linked immunosorbent assay (ELISA) was evaluated. Since the assay could easily be adapted to the assessment of the complex of tPA with its type-1 in...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690353
更新日期:1999-04-01 00:00:00
abstract::Epidermal growth factor receptor (EGFR) mutations are strong determinants of tumour response to EGFR tyrosine kinase inhibitors in non-small-cell lung cancer (NSCLC). Pleural effusion is a common complication of lung cancer. In this study, we assessed the feasibility of detection of EGFR mutations in samples of pleura...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603428
更新日期:2006-11-20 00:00:00
abstract:BACKGROUND:Enzastaurin, an oral serine-threonine kinase inhibitor, was initially developed as an ATP-competitive selective inhibitor against protein kinase Cβ. However, the mechanism by which enzastaurin contributes to tumourigenesis remains unclear. METHODS:We analysed the anti-tumour effects of enzastaurin in 22 lun...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.7
更新日期:2012-02-28 00:00:00
abstract::Eighteen patients with inoperable hepatocellular carcinoma (HCC) were treated with intrahepatic arterial yttrium-90 microspheres. All these patients showed a lung shunting below 15% and a tumour-to-normal ratio higher than 2 as determined by diagnostic technetium-99m macroaggregated albumin (Tc-MAA) gamma scintigraphy...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
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更新日期:1994-11-01 00:00:00
abstract::Little is known about chemoradiotherapy (CRT) in elderly patients with a locally advanced oesophageal cancer (OC). The aim of our study was to evaluate the tolerance and the outcome of elderly patients older than 70 years treated with CRT for a non-metastatic OC. Chemoradiotherapy was based on radiotherapy combined wi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604749
更新日期:2008-11-18 00:00:00
abstract::Changes in the buccal mucosa of 296 Indian and Malay betel-nut chewers in Perak, West Malaysia, were studied clinically. 167 out of 212 Indian subjects incorporated tobacco in their quids, while 45 out of 84 Malay subjects incorporated. "Gambir". The Indians appeared to show a higher proportion of mucosal changes, par...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1970.50
更新日期:1970-09-01 00:00:00
abstract:BACKGROUND:WFDC1/Prostate stromal 20 (ps20) is a small secreted protein highly expressed within the prostate stroma. WFDC1/ps20 expression is frequently downregulated or lost in prostate cancer (PCa) and ps20 has demonstrated growth-suppressive functions in numerous tumour model systems, although the mechanisms of this...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.91
更新日期:2016-05-24 00:00:00
abstract::Colorectal tumours from MYH polyposis patients display an excess of somatic G : C --> T : A transversions in the adenomatous polyposis coli gene. Here, we identify k-ras mutations in nine out of 54 (16.7%) MYH polyposis tumours. Their presence was associated with increased dysplasia and tubulovillous morphology (P=0.0...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601747
更新日期:2004-04-19 00:00:00
abstract::Malignant melanoma (MM) is thought to arise by sequential accumulation of genetic alterations in normal melanocytes. Previous cytogenetic and molecular studies indicated the 9p21 as the chromosomal region involved in MM pathogenesis. In addition to the CDKN genes (p16/CDKN2A, p15/CDKN2B and p19(ARF), frequently inacti...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2000.1513
更新日期:2000-12-01 00:00:00
abstract::The bioreductive antitumour agent, mitomycin C (MMC), requires activation by reductive enzymes like NAD(P)H:quinone oxidoreductase 1 (NQO1). We used a novel approach to increase MMC efficacy by selectively inducing NQO1 in tumour cells in vivo. CD-1 nude mice were implanted with HCT116 cells, and fed control diet or d...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602171
更新日期:2004-10-18 00:00:00
abstract:BACKGROUND:Epithelial ovarian cancer (EOC) cells are prone to metastasise throughout the peritoneal cavity. The epithelial-to-mesenchymal transition (EMT) is a necessary step towards metastatic tumour progression. CA125/MUC16 mucin is a high-molecular-weight glycoprotein overexpressed in the majority of serous carcinom...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.34
更新日期:2011-03-15 00:00:00
abstract:BACKGROUND:Dyskeratosis congenita 1 (DKC1) is dysregulated in several cancers. However, the expression and function of DKC1 in colorectal cancer (CRC) is rarely reported. METHODS:Tissue microarrays (TAMs) including 411 cases of CRC tissues and corresponding paracancerous tissues were used to examine the DKC1 expressio...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-019-0695-z
更新日期:2020-03-01 00:00:00
abstract::The prognostic value of flow cytometric parameters and tumour growth rate of melanoma metastases under the mouse renal capsule was investigated for tumours from 117 consecutive patients referred to the Helsinki University Central Hospital Melanoma Team. DNA flow cytometry (FCM) was interpretable for the tumours of 114...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.307
更新日期:1992-09-01 00:00:00
abstract:BACKGROUND:Epstein-Barr virus-positive post-transplant lymphoproliferative disease (PTLD) is a potentially lethal complication of iatrogenic immunosupression after transplantation. Predicting the development of PTLD allowing early and effective intervention is therefore of importance. Polymorphisms within cytokine gene...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605278
更新日期:2009-09-15 00:00:00
abstract::Data collected from lung cancer patients attending the Victoria Clinic of the British Columbia Cancer Agency are used to investigate how resources are rationed in the treatment of non-small-cell lung cancer (NSCLC). An ordered logit model is estimated to analyse empirically the relationship between treatment selection...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.136
更新日期:1996-03-01 00:00:00
abstract::PEP005 is a novel ingenol angelate that modulates protein kinases C (PKC) functions by activating PKC delta and inhibiting PKC alpha. This study assessed the antiproliferative effects of PEP005 alone and in combination with several other anticancer agents in a panel of 10 human cancer cell lines characterised for expr...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604642
更新日期:2008-12-02 00:00:00
abstract::Hepatic arterial floxuridine (HAI) in 35 patients with systemic fluorouracil/folinic acid-resistant colorectal liver metastases achieved a 14% partial response and 26% disease stabilization rate, with a median response duration of 7 months from onset of HAI. ...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1998.627
更新日期:1998-10-01 00:00:00
abstract::The expression of urokinase-type plasminogen activator (uPA) was investigated in squamous cell carcinoma of the human larynx. For this purpose, tissue extracts from 25 matched samples of normal mucosa and neoplastic larynx were compared for the levels of uPA activity as evaluated by a chromogenic PA assay and sodium d...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.512
更新日期:1996-10-01 00:00:00
abstract:BACKGROUND:Therapies targeting ERBB2 have shown success in the clinic. However, response is not determined solely by expression of ERBB2. Levels of ERBB3, its preferred heterodimerisation partner and ERBB ligands may also have a role. METHODS:We measured NRG1 expression by real-time quantitative RT-PCR and ERBB recept...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.39
更新日期:2011-03-29 00:00:00
abstract::Thirty patients with previously treated metastatic breast cancer were entered in a phase II study with oral lonidamine. Twenty-eight patients are evaluable for toxicity and 25 for response. A partial remission was obtained in four patients (16%) and disease stability in 11 (44%): 10 patients progressed (40%). Toxicity...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.51
更新日期:1989-02-01 00:00:00
abstract::To investigate the efficacy and safety of combining weekly oxaliplatin with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA) in treatment of patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. ...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1038/sj.bjc.6601985
更新日期:2004-08-02 00:00:00
abstract::In addition to the direct targeting effects on HER2-positive cells, trastuzumab may have a therapeutic role modulating the activity of the cellular immune system in patients with breast cancer. To investigate this further, the balance of T-regulatory (T(reg)), Th17, natural killer (NK) and NK T (NKT) cells before, dur...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604963
更新日期:2009-04-07 00:00:00
abstract:BACKGROUND:Non-persistence and non-compliance are common in women prescribed hormonal therapy for breast cancer, but little is known about their influence on recurrence. METHODS:A nested case-control study of associations between hormonal therapy non-persistence and non-compliance and the risk of early recurrence in w...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.518
更新日期:2013-09-17 00:00:00
abstract::The toxicity of misonidazole (1-(2-nitroimidazol-1-yl)-3-methoxy-2-propanol) towards mammalian cells in vitro has been determined as a function of O2 tension. Misonidazole under hypoxic conditions (less than 10 Parts/10(6) O2) shows the greatest toxicity. Split-dose experiments indicate that lethal damage can be "repa...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1978.172
更新日期:1978-07-01 00:00:00
abstract::Doxorubicin- and paclitaxel-selected variants of an in vitro invasive clonal population of the human breast cancer cell line, MDA-MB-435S, were established by pulse selection, and exhibited a novel 'superinvasive' phenotype. This phenotype is characterised by an ability to relocate to another surface following invasio...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602221
更新日期:2004-11-15 00:00:00