Correction: Molecular Subtypes in Head and Neck Cancer Exhibit Distinct Patterns of Chromosomal Gain and Loss of Canonical Cancer Genes.
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ABSTRACT:
SUBMITTER: Walter V
PROVIDER: S-EPMC5854434 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Publications
Correction: Molecular Subtypes in Head and Neck Cancer Exhibit Distinct Patterns of Chromosomal Gain and Loss of Canonical Cancer Genes.
Walter Vonn V Yin Xiaoying X Wilkerson Matthew D MD Cabanski Christopher R CR Zhao Ni N Du Ying Y Ang Mei Kim MK Hayward Michele C MC Salazar Ashley H AH Hoadley Katherine A KA Fritchie Karen K Sailey Charles J CJ Weissler Mark C MC Shockley William W WW Zanation Adam M AM Hackman Trevor T Thorne Leigh B LB Funkhouser William D WD Muldrew Kenneth L KL Olshan Andrew F AF Randell Scott H SH Wright Fred A FA Shores Carol G CG Hayes D Neil DN
PloS one 20180315 3
[This corrects the article DOI: 10.1371/journal.pone.0056823.]. ...[more]
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Project description:Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal heterogeneous disease. Beyond the role of human papilloma virus (HPV), no validated molecular characterization of the disease has been established. Using an integrated genomic analysis and validation methodology we confirm four molecular classes of HNSCC (basal, mesenchymal, atypical, and classical) consistent with signatures established for squamous carcinoma of the lung, including deregulation of the KEAP1/NFE2L2 oxidative stress pathway, differential utilization of the lineage markers SOX2 and TP63, and preference for the oncogenes PIK3CA and EGFR. For potential clinical use the signatures are complimentary to classification by HPV infection status as well as the putative high risk marker CCND1 copy number gain. A molecular etiology for the subtypes is suggested by statistically significant chromosomal gains and losses and differential cell of origin expression patterns. Model systems representative of each of the four subtypes are also presented.
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-03-01 | E-GEOD-39368 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2013-03-01 | GSE39368 | GEO
Project description:Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease whose underlying etiology has not been explained by traditional prognostic factors such as tumor site, stage, or histology. Although previous studies have shown that molecular subtypes of HNSCC exist, the benefit of such a classification scheme has not been fully realized. We show that molecular subtypes of HNSCC exist; that these subtypes have distinct patterns of chromosomal gain and loss, some of which affect canonical oncogenes and tumor suppressors; and that the subtypes are biologically and clinically relevant. These subtypes provide new insight into HNSCC etiology, as well as a valuable method for classifying HNSCC tumors. A total of 163 samples were considered. Quality control procedures were applied to microarray probe-level intensity files. A total of 138 tumor arrays remained after removing low-quality arrays, duplicate arrays, and arrays from non-HNSCC samples. The normexp background correction and loess normalization procedures were applied to the probe-level data. After log transformation, probes were matched to a common gene database to produce expression values for 15595 genes.
2013-03-01 | E-GEOD-39366 | biostudies-arrayexpress
Project description:Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease whose underlying etiology has not been explained by traditional prognostic factors such as tumor site, stage, or histology. Although previous studies have shown that molecular subtypes of HNSCC exist, the benefit of such a classification scheme has not been fully realized. We show that molecular subtypes of HNSCC exist; that these subtypes have distinct patterns of chromosomal gain and loss, some of which affect canonical oncogenes and tumor suppressors; and that the subtypes are biologically and clinically relevant. These subtypes provide new insight into HNSCC etiology, as well as a valuable method for classifying HNSCC tumors.
2013-03-01 | GSE39366 | GEO
Project description:BackgroundEpigenetic and genetic alteration plays a major role to the development of head and neck squamous cell carcinoma (HNSCC). Consumption of tobacco (smoking/chewing) and human papilloma virus (HPV) are also associated with an increase the risk of HNSCC. Promoter hypermethylation of the tumor suppression genes is related with transcriptional inactivation and loss of gene expression. We investigated epigenetic alteration (promoter methylation of tumor-related genes/loci) in tumor tissues in the context of genetic alteration, viral infection, and tobacco exposure and survival status.MethodologyThe study included 116 tissue samples (71 tumor and 45 normal tissues) from the Northeast Indian population. Methylation specific polymerase chain reaction (MSP) was used to determine the methylation status of 10 tumor-related genes/loci (p16, DAPK, RASSF1, BRAC1, GSTP1, ECAD, MLH1, MINT1, MINT2 and MINT31). Polymorphisms of CYP1A1, GST (M1 & T1), XRCC1and XRCC2 genes were studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiplex-PCR respectively.Principal findingsUnsupervised hierarchical clustering analysis based on methylation pattern had identified two tumor clusters, which significantly differ by CpG island methylator phenotype (CIMP), tobacco, GSTM1, CYP1A1, HPV and survival status. Analyzing methylation of genes/loci individually, we have found significant higher methylation of DAPK, RASSF1, p16 and MINT31 genes (P = 0.031, 0.013, 0.031 and 0.015 respectively) in HPV (+) cases compared to HPV (-). Furthermore, a CIMP-high and Cluster-1 characteristic was also associated with poor survival.ConclusionsPromoter methylation profiles reflecting a correlation with tobacco, HPV, survival status and genetic alteration and may act as a marker to determine subtypes and patient outcome in HNSCC.
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Project description:Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease whose underlying etiology has not been explained by traditional prognostic factors such as tumor site, stage, or histology. Although previous studies have shown that molecular subtypes of HNSCC exist, the benefit of such a classification scheme has not been fully realized. We show that molecular subtypes of HNSCC exist; that these subtypes have distinct patterns of chromosomal gain and loss, some of which affect canonical oncogenes and tumor suppressors; and that the subtypes are biologically and clinically relevant. These subtypes provide new insight into HNSCC etiology, as well as a valuable method for classifying HNSCC tumors. A total of 141 samples were considered. CEL files were subject to quality control (QC) procedures using the Affymetrix Genotyping Console, and arrays that produced contrast QC measurements above the default threshold of .4 were removed from subsequent analysis. The remaining 99 CEL files were processed with aroma, and log2 intensity ratios were produced using a pooled collection of normal samples as a reference. After segmenting the log2 ratios with DNAcopy, the resulting copy number profiles were subjected to manual review. Arrays that produced low quality copy number profiles were removed from subsequent analysis. Copy number values from chr1 - chr22 were considered.
2013-03-01 | E-GEOD-39367 | biostudies-arrayexpress
Project description:Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease whose underlying etiology has not been explained by traditional prognostic factors such as tumor site, stage, or histology. Although previous studies have shown that molecular subtypes of HNSCC exist, the benefit of such a classification scheme has not been fully realized. We show that molecular subtypes of HNSCC exist; that these subtypes have distinct patterns of chromosomal gain and loss, some of which affect canonical oncogenes and tumor suppressors; and that the subtypes are biologically and clinically relevant. These subtypes provide new insight into HNSCC etiology, as well as a valuable method for classifying HNSCC tumors.
2013-03-01 | GSE39367 | GEO
Project description:Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive malignancies with complex phenotypic, etiological, biological, and clinical heterogeneities. Previous studies have proposed different clinically relevant subtypes of HNSCC, but little is known about its corresponding prognosis or suitable treatment strategy. Here, we identified 101 core genes from three prognostic pathways, including mTORC1 signaling, unfold protein response, and UV response UP, in 124 pairs of tumor and matched normal tissues of HNSCC. Moreover, we identified three robust subtypes associated with distinct molecular characteristics and clinical outcomes using consensus clustering based on the gene expression profiles of 944 HNSCC patients from four independent datasets. We then integrated the genomic information of The Cancer Genome Atlas (TCGA) HNSCC cohort to comprehensively evaluate the molecular features of different subtypes and screen for potentially effective therapeutic agents. Cluster 1 had more arrested oncogenic signaling, the highest immune cell infiltration, the highest immunotherapy and chemotherapeutic responsiveness, and the best prognosis. By contrast, Cluster 3 showed more activated oncogenic signaling, the lowest immune cell infiltration, the lowest immunotherapy and chemotherapy responsiveness, and the worst prognosis. Our findings corroborate the molecular diversity of HNSCC tumors and provide a novel classification strategy that may guide for prognosis and treatment allocation.
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Project description:Low body mass index (BMI) has been associated with risk of head-neck cancer (HNC), but prospective data are scarce. We investigated the association between BMI, BMI at age 20 years and change in BMI during adulthood with risk of HNC and HNC subtypes. 120,852 participants completed a questionnaire on diet and other cancer risk factors, including anthropometric measurements, at baseline in 1986. After 20.3 years of follow-up, 411 HNC (127 oral cavity cancer (OCC), 84 oro-/hypopharyngeal cancer (OHPC), and 197 laryngeal cancer (LC)) cases and 3,980 subcohort members were available for case-cohort analysis using Cox proportional hazards models. BMI at baseline was inversely associated with risk of HNC overall, with a multivariate rate ratio of 3.31 (95% CI 1.40-7.82) for subjects with a BMI < 18.5 kg/m(2), compared to participants with a BMI of 18.5 to 25 kg/m(2). Among HNC subtypes, this association was strongest for OCC and OHPC. The association between BMI at age 20 and HNC risk appeared to be positive. In this large prospective cohort study, we found an inverse association between BMI at baseline and HNC risk. For BMI at age 20, however, a positive rather than inverse association was found.
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