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Article

Chromosomal aberrations and prognosis in patients with concomitant chemoradiotherapy for resected head and neck cancer

  • Authors:
    • Sung‑Won Park
    • Young‑Hoon Joo
    • Seung‑Hyun Jung
    • Seon‑Hee Yim
    • In‑Chul Nam
    • Kwang‑Jae Cho
    • Min‑Sik Kim
    • Yeun‑Jun Chung
  • View Affiliations / Copyright

    Affiliations: Integrated Research Center for Genome Polymorphism College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137‑701, Republic of Korea, Department of Otolaryngology‑Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137‑040, Republic of Korea
  • Pages: 2207-2215
    |
    Published online on: January 26, 2016
       https://doi.org/10.3892/or.2016.4595
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Abstract

Although concomitant chemoradiotherapy (CCRT) has recently become a mainstay of a primary treatment modality in advanced head and neck squamous cell carcinoma (HNSCC), some of the patients experience CCRT failure. If we can predict the CCRT outcomes, we can reduce unnecessary CCRT avoiding risk of CCRT‑related complication. We aimed to identify genetic alteration markers related to treatment failure in HNSCC patients who underwent radical surgery and CCRT. Genome‑wide copy number alterations (CNAs) were analyzed in 18 HNSCC patients with (n=9) or without (n=9) recurrence using oligoarray‑comparative genomic hybridization and candidate CNAs were validated by quantitative RT‑PCR. A total of 15 recurrently altered regions (RARs) were identified in the 18 HNSCC cases. Among them, two RARs were significantly associated with CCRT‑failure: copy number gained RARs of 7p11.2 harboring EGFR (P=0.029) and 18p11.32 harboring TYMS gene (P=0.029). Three RARs (7p11.2, 9p21.3 and 18p11.32) were significantly associated with poor disease‑specific survival in univariate analysis, and 7p11.2 was consistently significant in the multivariate analysis (HR 40.68, P=0.003). In conclusion, we defined novel genomic alterations associated with CCRT‑failure: 7p11.2 (EGFR) and 18p11.32 (TYMS). Our results provide useful clues for the elucidation of the molecular pathogenesis of HNSCC and to predict CCRT‑failure.
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1 

Pignon JP, Bourhis J, Domenge C and Designé L: Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: Three meta-analyses of updated individual data. MACH-NC Collaborative Group Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet. 355:949–955. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Smith RV, Kotz T, Beitler JJ and Wadler S: Long-term swallowing problems after organ preservation therapy with concomitant radiation therapy and intravenous hydroxyurea: Initial results. Arch Otolaryngol Head Neck Surg. 126:384–389. 2000. View Article : Google Scholar : PubMed/NCBI

3 

Cinelli M, Magnelli L and Chiarugi V: Redundant down-regulation pathways for p53. Pharmacol Res. 37:83–85. 1998. View Article : Google Scholar : PubMed/NCBI

4 

Osman I, Sherman E, Singh B, Venkatraman E, Zelefsky M, Bosl G, Scher H, Shah J, Shaha A, Kraus D, et al: Alteration of p53 pathway in squamous cell carcinoma of the head and neck: Impact on treatment outcome in patients treated with larynx preservation intent. J Clin Oncol. 20:2980–2987. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Nam TK, Lee JH, Cho SH, Chung IJ, Ahn SJ, Song JY, Yoon MS, Chung WK and Nah BS: Low hMLH1 expression prior to definitive chemoradiotherapy predicts poor prognosis in esophageal squamous cell carcinoma. Cancer Lett. 260:109–117. 2008. View Article : Google Scholar

6 

Li SW, Wang H, Liu ML, Zhang HB, Xiang YQ, Lv X, Xia WX, Zeng MS, Mai HQ, Hong MH, et al: Positive effect of high RKIP expression on reduced distant metastasis by chemotherapy when combined with radiotherapy in locoregionally advanced nasopharyngeal carcinoma: A prospective study. Med Oncol. 30:3222013. View Article : Google Scholar

7 

Cheng SH, Jian JJ, Tsai SY, Chan KY, Yen LK, Chu NM, Tan TD, Tsou MH and Huang AT: Prognostic features and treatment outcome in locoregionally advanced nasopharyngeal carcinoma following concurrent chemotherapy and radiotherapy. Int J Radiat Oncol Biol Phys. 41:755–762. 1998. View Article : Google Scholar : PubMed/NCBI

8 

Chen C, Chen S, Le QT, Chen J, Chen Z and Li D, Zhou M and Li D: Prognostic model for distant metastasis in locally advanced nasopharyngeal carcinoma after concurrent chemoradiotherapy. Head Neck. 37:209–214. 2015. View Article : Google Scholar

9 

Wang TL, Diaz LA Jr, Romans K, Bardelli A, Saha S, Galizia G, Choti M, Donehower R, Parmigiani G, Shih IeM, et al: Digital karyotyping identifies thymidylate synthase amplification as a mechanism of resistance to 5-fluorouracil in metastatic colorectal cancer patients. Proc Natl Acad Sci USA. 101:3089–3094. 2004. View Article : Google Scholar : PubMed/NCBI

10 

van den Broek GB, Wreesmann VB, van den Brekel MW, Rasch CR, Balm AJ and Rao PH: Genetic abnormalities associated with chemoradiation resistance of head and neck squamous cell carcinoma. Clin Cancer Res. 13:4386–4391. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Przybytkowski E, Aguilar-Mahecha A, Nabavi S, Tonellato PJ and Basik M: Ultradense array CGH and discovery of micro-copy number alterations and gene fusions in the cancer genome. Methods Mol Biol. 973:15–38. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Joo YH, Park SW, Jung SH, Lee YS, Nam IC, Cho KJ, Park JO, Chung YJ and Kim MS: Recurrent loss of the FHIT gene and its impact on lymphatic metastasis in early oral squamous cell carcinoma. Acta Otolaryngol. 133:992–999. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Kim JH, Hu HJ, Yim SH, Bae JS, Kim SY and Chung YJ: CNVRuler: A copy number variation-based case-control association analysis tool. Bioinformatics. 28:1790–1792. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Jung SH, Yim SH, Hu HJ, Lee KH, Lee JH, Sheen DH, Lim MK, Kim SY, Park SW, Kim SH, et al: Genome-wide copy number variation analysis identifies deletion variants associated with ankylosing spondylitis. Arthritis Rheumatol. 66:2103–2112. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

16 

Oddone N, Morgan GJ, Palme CE, Perera L, Shannon J, Wong E, Gebski V and Veness MJ: Metastatic cutaneous squamous cell carcinoma of the head and neck: The Immunosuppression, Treatment, Extranodal spread, and Margin status (ITEM) prognostic score to predict outcome and the need to improve survival. Cancer. 115:1883–1891. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Bernaldo de Quirós S, Merlo A, Secades P, Zambrano I, de Santa María IS, Ugidos N, Jantus-Lewintre E, Sirera R, Suarez C and Chiara MD: Identification of TRPC6 as a possible candidate target gene within an amplicon at 11q21-q22.2 for migratory capacity in head and neck squamous cell carcinomas. BMC Cancer. 13:1162013. View Article : Google Scholar : PubMed/NCBI

18 

Shi ZZ, Shang L, Jiang YY, Hao JJ, Zhang Y, Zhang TT, Lin DC, Liu SG, Wang BS, Gong T, et al: Consistent and differential genetic aberrations between esophageal dysplasia and squamous cell carcinoma detected by array comparative genomic hybridization. Clin Cancer Res. 19:5867–5878. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Gao Z, Meng X, Mu D, Sun X and Yu J: Prognostic significance of epidermal growth factor receptor in locally advanced esophageal squamous cell carcinoma for patients receiving chemoradiotherapy. Oncol Lett. 7:1118–1122. 2014.PubMed/NCBI

20 

Szabó B, Nelhubel GA, Kárpáti A, Kenessey I, Jóri B, Székely C, Peták I, Lotz G, Hegedus Z, Hegedus B, et al: Clinical significance of genetic alterations and expression of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas. Oral Oncol. 47:487–496. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Chung CH, Ely K, McGavran L, Varella-Garcia M, Parker J, Parker N, Jarrett C, Carter J, Murphy BA, Netterville J, et al: Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas. J Clin Oncol. 24:4170–4176. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Wilson PM, Danenberg PV, Johnston PG, Lenz HJ and Ladner RD: Standing the test of time: Targeting thymidylate biosynthesis in cancer therapy. Nat Rev Clin Oncol. 11:282–298. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Johnston PG, Fisher ER, Rockette HE, Fisher B, Wolmark N, Drake JC, Chabner BA and Allegra CJ: The role of thymidylate synthase expression in prognosis and outcome of adjuvant chemotherapy in patients with rectal cancer. J Clin Oncol. 12:2640–2647. 1994.PubMed/NCBI

24 

Murata S, Adachi M, Kioi M, Torigoe S, Ijichi K, Hasegawa Y, Ogawa T, Bhayani MK, Lai SY, Mitsudo K, et al: Etodolac improves 5-FU sensitivity of head and neck cancer cells through inhibition of thymidylate synthase. Anticancer Res. 31:2893–2898. 2011.PubMed/NCBI

25 

Yeh KH, Shun CT, Chen CL, Lin JT, Lee WJ, Lee PH, Chen YC and Cheng AL: High expression of thymidylate synthase is associated with the drug resistance of gastric carcinoma to high dose 5-fluorouracil-based systemic chemotherapy. Cancer. 82:1626–1631. 1998. View Article : Google Scholar : PubMed/NCBI

26 

Yasumatsu R, Nakashima T, Uryu H, Ayada T, Wakasaki T, Kogo R, Masuda M, Fukushima M and Komune S: Correlations between thymidylate synthase expression and chemosensitivity to 5-fluorouracil, cell proliferation and clinical outcome in head and neck squamous cell carcinoma. Chemotherapy. 55:36–41. 2009. View Article : Google Scholar

27 

Sunwoo JB, Sun PC, Gupta VK, Schmidt AP, El-Mofty S and Scholnick SB: Localization of a putative tumor suppressor gene in the sub-telomeric region of chromosome 8p. Oncogene. 18:2651–2655. 1999. View Article : Google Scholar : PubMed/NCBI

28 

Ishwad CS, Shuster M, Bockmühl U, Thakker N, Shah P, Toomes C, Dixon M, Ferrell RE and Gollin SM: Frequent allelic loss and homozygous deletion in chromosome band 8p23 in oral cancer. Int J Cancer. 80:25–31. 1999. View Article : Google Scholar : PubMed/NCBI

29 

Toomes C, Jackson A, Maguire K, Wood J, Gollin S, Ishwad C, Paterson I, Prime S, Parkinson K, Bell S, et al: The presence of multiple regions of homozygous deletion at the CSMD1 locus in oral squamous cell carcinoma question the role of CSMD1 in head and neck carcinogenesis. Genes Chromosomes Cancer. 37:132–140. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Ma C, Quesnelle KM, Sparano A, Rao S, Park MS, Cohen MA, Wang Y, Samanta M, Kumar MS, Aziz MU, et al: Characterization CSMD1 in a large set of primary lung, head and neck, breast and skin cancer tissues. Cancer Biol Ther. 8:907–916. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Zhang R and Song C: Loss of CSMD1 or 2 may contribute to the poor prognosis of colorectal cancer patients. Tumour Biol. 35:4419–4423. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Kamal M, Shaaban AM, Zhang L, Walker C, Gray S, Thakker N, Toomes C, Speirs V and Bell SM: Loss of CSMD1 expression is associated with high tumour grade and poor survival in invasive ductal breast carcinoma. Breast Cancer Res Treat. 121:555–563. 2010. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Park SW, Joo YH, Jung SH, Yim SH, Nam IC, Cho KJ, Kim MS and Chung YJ: Chromosomal aberrations and prognosis in patients with concomitant chemoradiotherapy for resected head and neck cancer. Oncol Rep 35: 2207-2215, 2016.
APA
Park, S., Joo, Y., Jung, S., Yim, S., Nam, I., Cho, K. ... Chung, Y. (2016). Chromosomal aberrations and prognosis in patients with concomitant chemoradiotherapy for resected head and neck cancer. Oncology Reports, 35, 2207-2215. https://doi.org/10.3892/or.2016.4595
MLA
Park, S., Joo, Y., Jung, S., Yim, S., Nam, I., Cho, K., Kim, M., Chung, Y."Chromosomal aberrations and prognosis in patients with concomitant chemoradiotherapy for resected head and neck cancer". Oncology Reports 35.4 (2016): 2207-2215.
Chicago
Park, S., Joo, Y., Jung, S., Yim, S., Nam, I., Cho, K., Kim, M., Chung, Y."Chromosomal aberrations and prognosis in patients with concomitant chemoradiotherapy for resected head and neck cancer". Oncology Reports 35, no. 4 (2016): 2207-2215. https://doi.org/10.3892/or.2016.4595
Copy and paste a formatted citation
x
Spandidos Publications style
Park SW, Joo YH, Jung SH, Yim SH, Nam IC, Cho KJ, Kim MS and Chung YJ: Chromosomal aberrations and prognosis in patients with concomitant chemoradiotherapy for resected head and neck cancer. Oncol Rep 35: 2207-2215, 2016.
APA
Park, S., Joo, Y., Jung, S., Yim, S., Nam, I., Cho, K. ... Chung, Y. (2016). Chromosomal aberrations and prognosis in patients with concomitant chemoradiotherapy for resected head and neck cancer. Oncology Reports, 35, 2207-2215. https://doi.org/10.3892/or.2016.4595
MLA
Park, S., Joo, Y., Jung, S., Yim, S., Nam, I., Cho, K., Kim, M., Chung, Y."Chromosomal aberrations and prognosis in patients with concomitant chemoradiotherapy for resected head and neck cancer". Oncology Reports 35.4 (2016): 2207-2215.
Chicago
Park, S., Joo, Y., Jung, S., Yim, S., Nam, I., Cho, K., Kim, M., Chung, Y."Chromosomal aberrations and prognosis in patients with concomitant chemoradiotherapy for resected head and neck cancer". Oncology Reports 35, no. 4 (2016): 2207-2215. https://doi.org/10.3892/or.2016.4595
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