Prognostic significance of p16INK4a alterations and 9p21 loss of heterozigosity in locally advanced laryngeal squamous cell carcinoma
作者： Viviana Bazan , Ines Zanna , Manuela Migliavacca , Maria Teresa Sanz-Casla , Maria Luisa Maestro
DOI: 10.1002/JCP.10138
关键词:
摘要: The p16INK4a gene, localized within chromosome 9p21, has been identified as a cyclin-dependent kinase inhibitor and may negatively regulate the cell cycle acting tumor suppressor. Genetic alterations involving 9p21 region are common in human cancers. A consecutive series of 64 untreated patients (median follow up 53 months) undergoing surgical resection for locally advanced laryngeal squamous-cell carcinomas (LSCCs) studied prospectively. Our purpose was to investigate p16 (9p21 allelic loss, hypermethylation point mutations) their possible association with clinico-pathological data flow cytometric variables (DNA-ploidy S-phase fraction (SPF)), determine prognostic role this gene these tumors. PCR-based techniques were used investigating loss heterozygosity (LOH) methylation promoter status gene. mutations detected by PCR-SSCP (single strand conformation polymorphism) sequencing. LOH 16/62 (26%) informative tumors, 5% (3/64) 9% (6/64) cases. significantly associated high SPF DNA-aneuploidy. By univariate analysis, poor histologic differentiation, stage IV, DNA-aneuploidy proved be related quicker relapse, whereas same factors, addition SPF, any shorter overall survival. Cox proportional hazards analysis only grade (G3) independently both disease relapse death. study important biomolecular indicators LSCCs.
sci-hub.se 参考文章(52)
Ichimura K, Schmidt Ee, Yamaguchi N, James Cd, Collins Vp, A Common Region of Homozygous Deletion in Malignant Human Gliomas Lies between the IFNα/ω Gene Cluster and the D9S171 Locus Cancer Research. ,vol. 54, pp. 3127- 3130 ,(1994)
Tetsuro Nishihira, Shozo Mori, Koh Miura, Yusuke Nakamura, Takahisa Aoki, Takahiro Mori, Frequent somatic mutation of the MTS1/CDK4I (multiple tumor suppressor/cyclin-dependent kinase 4 inhibitor) gene in esophageal squamous cell carcinoma. Cancer Research. ,vol. 54, pp. 3396- 3397 ,(1994)
Adriaan de Bruïne, Anton de Goeij, Joop ten Kate, Marjolein van Driel, Peter Moerkerk, Jan Willem Arends, Type and Number of Ki-ras Point Mutations Relate to Stage of Human Colorectal Cancer Cancer Research. ,vol. 54, pp. 3376- 3378 ,(1994)
David R. Cox, Regression Models and Life-Tables Springer Series in Statistics. ,vol. 34, pp. 527- 541 ,(1992) , 10.1007/978-1-4612-4380-9_37
David Sidransky, Geoffrey I. Shapiro, Christian D. Edwards, Li Mao, Barrett J. Rollins, Gauri Bedi, Adrian Merlo, A Novel p16INK4A Transcript Cancer Research. ,vol. 55, pp. 2995- 2997 ,(1995)
Frederich Y. Luh, Sharon J. Archer, Peter J. Domaille, Brian O. Smith, Darerca Owen, Deborah H. Brotherton, Andrew R. C. Raine, Xu Xu, Leonardo Brizuela, Stephen L. Brenner, Ernest D. Laue, Structure of the cyclin-dependent kinase inhibitor p19Ink4d. Nature. ,vol. 389, pp. 999- 1003 ,(1997) , 10.1038/40202
Brian G. Gabrielli, Marilyn K. Walters, Pamela M. Pollock, Marina Castellano, Louise M. Down, Nicholas K. Hayward, Peter G. Parsons, Louise E. Sparrow, CDKN2A/p16 Is Inactivated in Most Melanoma Cell Lines Cancer Research. ,vol. 57, pp. 4868- 4875 ,(1997)
Yingshe Zhao, Sizhong Zhang, Buyin Fu, Cuiying Xiao, Abnormalities of Tumor Suppressor Genes P16 and P15 in Primary Maxillofacial Squamous Cell Carcinomas Cancer Genetics and Cytogenetics. ,vol. 112, pp. 26- 33 ,(1999) , 10.1016/S0165-4608(98)00259-3
Pedro Jares, Alfons Nadal, Pedro L Fernández, Magda Pinyol, Lluis Hernández, Maite Cazorla, Silvia Hernández, Silvia Beà, Antonio Cardesa, Elías Campo, None, Disregulation of p16MTS1/CDK4I protein and mRNA expression is associated with gene alterations in squamous-cell carcinoma of the larynx. International Journal of Cancer. ,vol. 81, pp. 705- 711 ,(1999) , 10.1002/(SICI)1097-0215(19990531)81:5<705::AID-IJC6>3.0.CO;2-W
Pascal Chaubert, Nathalie Burri, Phillip Shaw, Hanifa Bouzourene, Isabelle Sordat, Bernard Sordat, Michel Gillet, Daniel Schorderet, Fred T Bosman, Methylation silencing and mutations of the p14ARF and p16INK4a genes in colon cancer. Laboratory Investigation. ,vol. 81, pp. 217- 229 ,(2001) , 10.1038/LABINVEST.3780230