Analysis of gene copy number changes in head and neck cancer

2018 ◽  
Vol 43 (4) ◽  
pp. 1004-1009 ◽  
Author(s):  
E. Baltaci ◽  
E. Karaman ◽  
N. Dalay ◽  
N. Buyru
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Copy Number Changes

scholarly journals Induction Docetaxel, Cisplatin, and Cetuximab Followed by Concurrent Radiotherapy, Cisplatin, and Cetuximab and Maintenance Cetuximab in Patients With Locally Advanced Head and Neck Cancer

2010 ◽  
Vol 28 (36) ◽  
pp. 5294-5300 ◽  
Author(s):  
Athanassios Argiris ◽  
Dwight E. Heron ◽  
Ryan P. Smith ◽  
Seungwon Kim ◽  
Michael K. Gibson ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Locally Advanced ◽  
Gene Copy Number ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Gene Copy ◽  
Term Survival

PurposeWe incorporated cetuximab, a chimeric monoclonal antibody against the epidermal growth factor receptor (EGFR), into the induction therapy and subsequent chemoradiotherapy of head and neck cancer (HNC).Patients and MethodsPatients with locally advanced HNC, including squamous and undifferentiated histologies, were treated with docetaxel 75 mg/m2day 1, cisplatin 75 mg/m2day 1, and cetuximab 250 mg/m2days 1, 8, and 15 (after an initial loading dose of 400 mg/m2), termed TPE, repeated every 21 days for three cycles, followed by radiotherapy with concurrent cisplatin 30 mg/m2and cetuximab weekly (XPE), and maintenance cetuximab for 6 months. Quality of life (QOL) was assessed using Functional Assessment of Cancer Therapy–Head and Neck. In situ hybridization (ISH) for human papillomavirus (HPV), immunohistochemistry for p16, and fluorescence ISH for EGFR gene copy number were performed on tissue microarrays.ResultsOf 39 enrolled patients, 36 had stage IV disease and 23 an oropharyngeal primary. Acute toxicities during TPE included neutropenic fever (10%) and during XPE, grade 3 or 4 oral mucositis (54%) and hypomagnesemia (39%). With a median follow-up of 36 months, 3-year progression-free survival and overall survival were 70% and 74%, respectively. Eight patients progressed in locoregional sites, three in distant, and one in both. HPV positivity was not associated with treatment efficacy. No progression-free patient remained G-tube dependent. The H&N subscale QOL scores showed a significant decrement at 3 months after XPE, which normalized at 1 year.ConclusionThis cetuximab-containing regimen resulted in excellent long-term survival and safety, and warrants further evaluation in both HPV-positive and -negative HNC.

scholarly journals Decomposing the subclonal structure of tumors with two-way mixture models on copy number aberrations

2018 ◽  
Author(s):  
An-Shun Tai ◽  
Chien-Hua Peng ◽  
Shih-Chi Peng ◽  
Wen-Ping Hsieh
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Copy Number ◽  
Tumor Heterogeneity ◽  
Tumor Evolution ◽  
Depth Information ◽  
Sequencing Data ◽  
Single Nucleotide Variants ◽  
Copy Number Aberrations

AbstractMultistage tumorigenesis is a dynamic process characterized by the accumulation of mutations. Thus, a tumor mass is composed of genetically divergent cell subclones. With the advancement of next-generation sequencing (NGS), mathematical models have been recently developed to decompose tumor subclonal architecture from a collective genome sequencing data. Most of the methods focused on single-nucleotide variants (SNVs). However, somatic copy number aberrations (CNAs) also play critical roles in carcinogenesis. Therefore, further modeling subclonal CNAs composition would hold the promise to improve the analysis of tumor heterogeneity and cancer evolution. To address this issue, we developed a two-way mixture Poisson model, named CloneDeMix for the deconvolution of read-depth information. It can infer the subclonal copy number, mutational cellular prevalence (MCP), subclone composition, and the order in which mutations occurred in the evolutionary hierarchy. The performance of CloneDeMix was systematically assessed in simulations. As a result, the accuracy of CNA inference was nearly 93% and the MCP was also accurately restored. Furthermore, we also demonstrated its applicability using head and neck cancer samples from TCGA. Our results inform about the extent of subclonal CNA diversity, and a group of candidate genes that probably initiate lymph node metastasis during tumor evolution was also discovered. Most importantly, these driver genes are located at 11q13.3 which is highly susceptible to copy number change in head and neck cancer genomes. This study successfully estimates subclonal CNAs and exhibit the evolutionary relationships of mutation events. By doing so, we can track tumor heterogeneity and identify crucial mutations during evolution process. Hence, it facilitates not only understanding the cancer development but finding potential therapeutic targets. Briefly, this framework has implications for improved modeling of tumor evolution and the importance of inclusion of subclonal CNAs.

Array rank order regression analysis for the detection of gene copy-number changes in human cancer

Genomics ◽  
2003 ◽  
Vol 82 (2) ◽  
pp. 122-129 ◽  
Author(s):  
Chun Cheng ◽  
Robert Kimmel ◽  
Paul Neiman ◽  
Lue Ping Zhao
Keyword(s):  
Regression Analysis ◽  
Copy Number ◽  
Human Cancer ◽  
Rank Order ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Copy Number Changes

scholarly journals Detection of gene copy number changes in CGH microarrays using a spatially correlated mixture model

2006 ◽  
Vol 22 (8) ◽  
pp. 911-918 ◽  
Author(s):  
Philippe Broët ◽  
Sylvia Richardson
Keyword(s):  
Mixture Model ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Spatially Correlated ◽  
Copy Number Changes

scholarly journals Characterization of a head and neck cancer-derived cell line panel confirms the distinct TP53-proficient copy number-silent subclass

Oral Oncology ◽  
2019 ◽  
Vol 98 ◽  
pp. 53-61 ◽  
Author(s):  
Anne M. van Harten ◽  
Jos B. Poell ◽  
Marijke Buijze ◽  
Arjen Brink ◽  
Susanne I. Wells ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Cell Line ◽  
Neck Cancer ◽  
Copy Number ◽  
Cell Line Panel

Abstract A60: Analysis of gene copy number changes in chronic lymphocytic leukemia

2013 ◽  
Author(s):  
Nejat Dalay ◽  
Mustafa Isin ◽  
Guven Cetin ◽  
Melih Aktan
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Copy Number ◽  
Gene Copy Number ◽  
Lymphocytic Leukemia ◽  
Gene Copy ◽  
Copy Number Changes

Identification of Novel Genetic Lesions in Myelodysplastic Syndromes Using High Density SNP-Arrays.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2430-2430
Author(s):  
Saskia Langemeijer ◽  
Roland Kuiper ◽  
Peter Vandenberghe ◽  
Estelle Verburgh ◽  
Jan Boezeman ◽  
...  
Keyword(s):  
Copy Number ◽  
Single Gene ◽  
Snp Array ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Trisomy 8 ◽  
Entire Genome ◽  
Monosomy 7 ◽  
Snp Arrays ◽  
Copy Number Changes

Abstract Conventional cytogenetics and FISH reveal chromosomal defects in approximately 50% of MDS patients. These mostly consist of gross gains and losses of specific chromosomal regions or entire chromosomes like 5q-, monosomy 7 and trisomy 8. Currently, the genes that are critical for MDS development remain largely unknown, which hampers both a proper diagnosis of clonal disease as well as development of targeted therapy. To identify the affected genetic loci and to map the critical regions and genes in MDS, we performed high-resolution (250k) SNP-based CGH. So far, 231 controls and 87 MDS patients from various subclasses were analyzed. In all patients and controls, loss of heterozygosity (LOH) without copy number changes was observed at multiple loci across the entire genome. Although large areas of LOH encompassing the main part of the p- or q-arm of chromosomes were only seen in MDS patients, no genomic regions were identified that were statistically more often affected in patients compared to control DNA. Copy number changes (excluding known regions of normal variation) were seen in 53% of patients with a normal karyotype (n=54). In 231 controls and in non-malignant T cells of a subset of patients, these areas were not affected, indicating that they were disease-specific. The number of affected regions per patient ranged from 0–7. The majority (82%) of karyotypic aberrations were confirmed using SNP-arrays. Only balanced translocations and some subclonal aberrations could not be detected. Importantly, SNP-array analysis revealed additional copy number changes in 70% of patients with an abnormal karyotype. Copy number changes that were observed in only one patient might reflect general genomic instability in the tumor cells and may not represent genes that are implicated in the pathogenesis of MDS. Therefore, we selected areas that were affected in at least two patients. In total, we found 51 different recurrent genomic loci. This indicates that MDS is genetically diverse, which is in agreement with its diverse clinical and morphological presentation. Among the 51 recurrent loci, 15 contained only a single gene (Table). Among these genes, there were several known to be implicated in MDS (e.g. ETV6 and RUNX1), whereas others represent novel genes that are potentially implicated in the pathogenesis of MDS. For several of these, a biological function has been described that may be linked to control of differentiation and proliferation, like the transcription- and proliferation-regulating gene JARID2 and the transcription factor DMTF1. Currently, we are performing a high thoughput mutation- and expression-analysis of these genes in a larger group of patients. Single gene copy number changes in MDS Chr Cytoband Loss/Gain Cases Size (Mb) Gene 1 p35.1 loss 2 0.01 CSMD2 3 p24.2 loss 2 0.07 LRRC3B 6 p22.3 loss 3 0.02 JARID2 8 p23.2-1 gain 2 0.14 MCPH1 9 p13.2 gain 2 0.23 MELK 9 p24.3 gain 2 1.14 SMARCA2 11 q22.3 gain 2 0.05 SLC35F2 12 p12.1 loss 3 0.08 ST8SIA1 12 p13.2 loss 4 0.08 ETV6 12 q23.2 loss 2 0.03 IGF1 16 q23.3 loss 2 0.06 MPHOSPH6 21 q22.12 loss 3 0.07 RUNX1 21 q22.2 gain 2 0.62 DSCAM 22 q12.2 gain 2 0.00 PES1 X q13.1 loss 2 0.17 EDA

EGF-r gene copy number changes in renal cell carcinoma detected by fluorescencein situ hybridization

1998 ◽  
Vol 184 (4) ◽  
pp. 424-429 ◽  
Author(s):  
Holger Moch ◽  
Guido Sauter ◽  
Thomas C. Gasser ◽  
Lukas Bubendorf ◽  
Jan Richter ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Fluorescencein Situ Hybridization ◽  
R Gene ◽  
Copy Number Changes

Frequent gene copy number changes and BRAF V600E gene mutation in conjunctival melanoma

2010 ◽  
Vol 88 ◽  
pp. 0-0
Author(s):  
F JMOR ◽  
SL LAKE ◽  
AFG TAKTAK ◽  
BE DAMATO ◽  
SE COUPLAND
Keyword(s):  
Gene Mutation ◽  
Copy Number ◽  
Gene Copy Number ◽  
Braf V600e ◽  
Gene Copy ◽  
Conjunctival Melanoma ◽  
Copy Number Changes
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