Identification of genomic copy number variations associated with specific clinical features of head and neck cancer

Abstract

BackgroundCopy number variations (CNSs) of large genomic regions are an important mechanism implicated in the development of head and neck cancer, however, for most changes their exact role is not well understood. The aim of this study was to find possible associations between gains/losses of genomic regions and clinically distinct subgroups of head and neck cancer patients.ResultsArray comparative genomic hybridization (aCGH) analysis was performed on DNA samples in 64 patients with cancer in oral cavity, oropharynx or hypopharynx. Overlapping genomic regions created from gains and losses were used for statistical analysis. Following regions were overrepresented: in tumors with stage I or II a gain of 2.98 Mb on 6p21.2-p11 and a gain of 7.4 Mb on 8q11.1-q11.23; in tumors with grade I histology a gain of 1.1 Mb on 8q24.13, a loss of a large part of p arm of chromosome 3, a loss of a 1.24 Mb on 6q14.3, and a loss of terminal 32 Mb region of 8p23.3; in cases with affected lymph nodes a gain of 0.75 Mb on 3q24, and a gain of 0.9 Mb on 3q26.32-q26.33; in cases with unaffected lymph nodes a gain of 1.1 Mb on 8q23.3, in patients not treated with surgery a gain of 12.2 Mb on 7q21.3-q22.3 and a gain of 0.33 Mb on 20q11.22.ConclusionsOur study identified several genomic regions of interest which appear to be associated with various clinically distinct subgroups of head and neck cancer. They represent a potentially important source of biomarkers useful for the clinical management of head and neck cancer. In particular, the PIK3CA and AGTR1 genes could be singled out to predict the lymph node involvement.

Association of Inherited Copy Number Variation in ADAM3A and ADAM5 Pseudogenes with Oropharynx Cancer Risk and Outcome

“…Somatic CNVs have been more studied in general HNSCC than inherited ones. For instance, somatic cells of OPSCC featured focal amplification of the 3q26-28 region, containing the transcription factor genes TP63 and SOX2 , and PIK3CA oncogene [ 11 , 12 ]; the 11q13 region, containing the cell cycle regulator gene CCND1 , the tumor suppressor gene FADD , and the CTTN oncogene [ 11 , 13 ]; the 11q22 region, containing the BIRC2 and YAP1 oncogenes; and the 20q11.22 region, containing the cell cycle regulator gene E2F1 [ 11 ]. Somatic cells of OPSCC also featured loss of the 14q32.31 region, containing the TRAF3 gene, involved in antiviral immune response [ 11 ]; and loss of the 4q35.2, 5q35.3, 9p21.3, 9q34.3, 17p13.1, and 18q21.2 regions, containing the FAT1 , NSD1 , CDKN2A , NOTCH1 , TP53 , and SMAD4 tumor suppressor genes, respectively [ 11 , 14 , 15 ].…”