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. 2009 May;135(5):703-13.
doi: 10.1007/s00432-008-0507-y. Epub 2008 Nov 8.

Frequent deletion of ING2 locus at 4q35.1 associates with advanced tumor stage in head and neck squamous cell carcinoma

Silvia S Borkosky  1 , Mehmet Gunduz, Hitoshi Nagatsuka, Levent Bekir Beder, Esra Gunduz, Mahmoud A L Sheikh Ali, Andrea P Rodriguez, Mehmet Zeynel Cilek, Susumu Tominaga, Noboru Yamanaka, Kenji Shimizu, Noriyuki Nagai
Affiliations

Frequent deletion of ING2 locus at 4q35.1 associates with advanced tumor stage in head and neck squamous cell carcinoma

Silvia S Borkosky et al. J Cancer Res Clin Oncol. 2009 May.

Abstract

Background: Loss of heterozygosity (LOH) in the ING family members has been shown in head and neck squamous cell carcinoma (HNSCC) except for ING2. Like all the other members of ING family, ING2, which is located at chromosome 4q35.1, is a promising tumor suppressor gene (TSG). In this study, we performed LOH analysis of ING2 in HNSCC and compared it with clinicopathological variables.

Materials and methods: We performed LOH analysis in DNAs from 80 paired of normal and HNSCC tissues, using a specifically designed microsatellite marker on chromosome 4q35.1, which detects allelic loss of ING2. TP53 mutation analysis and its relationship with ING2 chromosomal deletion were also performed in available 68 of the samples. The correlation between LOH status and clinicopathological characteristics was evaluated by using statistical methods. The overall survival (OS) and disease free survival (DFS) were also determined.

Results: LOH was detected in 54.6% (30/55) of the informative samples. Statistical significance was obtained between LOH and tumor (T) stage (P = 0.02), application of radiotherapy and chemotherapy. Positive node status (N) appeared to be the only independent prognostic factor for both OS (P = 0.031) and DFS (P = 0.044).

Conclusions: Our study showed allelic loss of 4q35.1 in HNSCC. The high percentage of LOH suggests ING2 as a candidate TSG in HNSCC. High LOH frequency was statistically associated with advanced T stage, suggesting that ING2 LOH might occur in late stages during HNSCC progression.

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Figures

Fig. 1
Fig. 1
LOH analysis on chromosme 4q35.1 in HNSCC. a Schematic representation of LOH distribution. Filled box LOH, open box retention of heterozygosity, shaded box not informative (homozygous). b Representative results of microsatellite analysis. DNAs of tumor (T) and corresponding normal (N) tissues are shown with case numbers on the top. Arrows depict lost alleles in the samples with LOH. Case 75 shows retention of heterozygosity. Case 5 is not informative (homozygous)
Fig. 2
Fig. 2
A physical map of the ING2MS location. The location of the marker and genes are based upon the latest mapping information derived from the National Center for Biotechnology Information (NCBI) and the Genome Database (GDB) homepages (http://www.ncbi.nlm.nih.gov/genome/guide/human/, http://www.gdb.org/)
Fig. 3
Fig. 3
Overall and disease-free survivals in the groups of HNSCC patients with ING2 LOH and retention of heterozygosity. Kaplan–Meier survival curves for the total number of cases (n = 74) stratified by ING2 LOH. The cases were divided into LOH positive (+) and LOH negative (−) (retention). Statistical significance was defined as P < 0.05. a The mean disease-free survival in the LOH (+) group was 27 ± 6 months (95% CI: 15–38 months) and in the LOH (−) group was 41 ± 7 months (95% CI: 28–54 months) (P = 0.11). b The mean overall survival in the LOH group was 43 ± 5 months (95% CI: 32–54 months) and in the retention group was 49 ± 6 months (95% CI: 38–61 months) (P = 0.52)
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References

    1. Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, van Tuinen P, Ledbetter DH, Barker DF, Nakamura Y, White R, Vogelstein B (1989) Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244(4901):217–221. doi:10.1126/science.2649981 - PubMed
    1. Beder LB, Gunduz M, Ouchida M, Gunduz E, Sakai A, Fukushima K, Nagatsuka H, Ito S, Honjo N, Nishizaki K, Shimizu K (2006) Identification of a candidate tumor suppressor gene RHOBTB1 located at a novel allelic loss region 10q21 in head and neck cancer. J Cancer Res Clin Oncol 132(1):19–27. doi:10.1007/s00432-005-0033-0 - PMC - PubMed
    1. Bradford CR, Zhu S, Poore J, Fisher SG, Beals TF, Thoraval D, Hanash SM, Carey TE, Wolf GT (1997) p53 mutation as a prognostic marker in advanced laryngeal carcinoma. Department of Veterans Affairs Laryngeal Cancer Cooperative Study Group. Arch Otolaryngol Head Neck Surg 123(6):605–609 - PubMed
    1. Cabelguenne A, Blons H, de Waziers I, Carnot F, Houllier AM, Soussi T, Brasnu D, Beaune P, Laccourreye O, Laurent-Puig P (2000) p53 alterations predict tumor response to neoadjuvant chemotherapy in head and neck squamous cell carcinoma: a prospective series. J Clin Oncol 18(7):1465–1473 - PubMed
    1. Cengiz B, Gunduz M, Nagatsuka H, Beder L, Gunduz E, Tamamura R, Mahmut N, Fukushima K, Ali MA, Naomoto Y, Shimizu K, Nagai N (2007) Fine deletion mapping of chromosome 2q21-37 shows three preferentially deleted regions in oral cancer. Oral Oncol 43(3):241–247. doi:10.1016/j.oraloncology.2006.03.004 - PubMed

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