Integrated analysis revealing genome‑wide chromosomal copy number variation in supraglottic laryngeal squamous cell carcinoma

Abstract

Laryngeal squamous cell carcinoma (LSCC) is a genetically complex tumor type and one of the leading causes of cancer-associated disability and mortality. Genetic instability, such as chromosomal instability, is associated with the tumorigenesis of LSCC. Copy number variations (CNVs) have been demonstrated to contribute to the genetic diversity of tumor pathogenesis. Comparative genomic hybridization (CGH) has emerged as a high-throughput genomic technology that facilitates the aggregation of high-resolution data of cancer-associated genomic imbalances. In the present study, a total of 38 primary supraglottic LSCC cases were analyzed by high-resolution array-based CGH (aCGH) to improve the understanding of the genetic alterations in LSCC. Additionally, integration with bioinformatic analysis of microarray expression profiling data from the Gene Expression Omnibus (GEO) database provided a fundamental method for the identification of putative target genes. Genomic CNVs were detected in all cases. The size of net genomic imbalances per case ranged between a loss of 682.3 Mb (~24% of the genome) and a gain of 1,958.6 Mb (~69% of the genome). Recurrent gains included 2pter-q22.1, 3q26.1-qter, 5pter-p12, 7p22.3p14.1, 8p12p11.22, 8q24.13q24.3, 11q13.2q13.4, 12pter-p12.2, 18pter-p11.31 and 20p13p12.1, whereas recurrent losses included 3pter-p21.32, 4q28.1-q35.2, 5q13.2-qter, 9pter-p21.3 and monosomy 13. Gains of 3q26.1-qter were associated with tumor stage, poor differentiation and smoking history. Additionally, through integration with bioinformatic analysis of data from the GEO database, putative target oncogenes, including sex-determining region Y-box 2, eukaryotic translation initiation factor 4 gamma 1, fragile X-related gene 1, disheveled segment polarity protein 3, defective n cullin neddylation 1 domain containing 1, insulin like growth factor 2 mRNA binding protein 2 and CCDC26 long non-coding RNA, and tumor suppressor genes, such as CUB and sushi multiple domains 1, cyclin dependent kinase inhibitor 2A, protocadherin 20, serine peptidase inhibitor Kazal type 5 and Nei like DNA glycosylase 3, were identified in supraglottic LSCC. Supraglottic LSCC is a genetically complex tumor type and aCGH was demonstrated to be effective in the determination of molecular profiles with higher resolution. The present results enable the identification of putative target oncogenes and tumor suppressor gene mapping in supraglottic LSCC.

Multi-Omics Analysis of the Effects of Smoking on Human Tumors

“…The gain of the 3q26 locus was remarkably related to the occurrence of human squamous cell carcinoma, including LUSC and HNSC. Hence, the gain of 3q26 was significantly associated with smoking ( Li et al, 2020a ). CDKN2A (9p21.3) encodes P16 protein that is a tumor suppressor.…”

Prenatal diagnosis and counseling of fetal chromosomes with structural abnormalities

“…Case 3 was short arm deletion on chromosome 16 and long arm duplication on part of chromosome 18, related to this study, Al-Qattan MM [14] found that a boy with continuous deletion of SLX4, DNASE1, TRAP1 and CREBBP genes at 16p13.3 had a wide thumb with radial angulation, mild intellectual impairment, mild facial deformity and hydronephrosis were found in this case, and the CMA results of case 3 were basically consistent with the description of symptoms, the literature on 18q12.3q23 was rarely repeated, and no relevant studies were found. In case 4, the short arm region of chromosome 20 was repeated at the long arm position of chromosome 9, there are few literatures on the ampli cation of 20p13p12.1, Li D [15] found that the CMA result of a laryngeal cancer patient was 20p13p12.1. Pachajoa H[16] found that a baby girl was diagnosed with right megaloureter 2 months after birth, and was diagnosed with mild mental retardation and slow cognitive rhythm at the age of 3, physical examination at the age of 17 revealed a round face, broad nose, xanthoxanoma of both lower eyelids, fold of inner canthus, long eyelid clefs, slow speech, poor coordination and thick hands, this case was partially consistent with the CMA results of Case 4.…”

The Roles of the Fluorescent In Situ Hybridization (FISH) and Comparative Genomic Hybridization (CGH) Techniques in the Detection of the Breast Cancer

“…Comparative genomic hybridization (CGH) has emerged to promote the aggregation of high-resolution data of cancer-associated genomic imbalances as a highthroughput genomic technology. High-resolution genomic microarray CGH (Li et al, 2020). The rapidly growing CGH publication database already contains around 1500 tumours and is beginning to reveal genetic anomalies characteristic of certain forms of tumour or stages of tumour progression (Forozan et al,1997).…”