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Delineating Genetic Pathways of Disease Progression in Head and Neck Squamous Cell Carcinoma
Maria J. Worsham, PhD;
Gerard Pals, PhD;
Jan P. Schouten, PhD;
Rosalind M. L. van Spaendonk, PhD;
Adriane Concus, MD;
Thomas E. Carey, PhD;
Michael S. Benninger, MD
Arch Otolaryngol Head Neck Surg. 2003;129:702-708.
Objective To identify altered gene targets that characterize disease progression in squamous cell carcinoma (SCC) of the head and neck (HNSCC). Genetic alterations in HNSCC cell lines reflect the tumor in vivo and can serve as valuable tools to study the development and progression of HNSCC. Identification of key molecular events may be useful for more accurate distinction of prognostic groups for selection and targeting of therapy.
Design Individual gene loci were analyzed for genetic alterations using a novel genomewide strategy.
Subjects Head and neck squamous cell carcinoma primary (A) and recurrent or metastatic (B) cell lines UMSCC-11A/11B, UMSCC-17A/17B (previously karyotyped), and UMSCC-81A/81B are described.
Results At the genome level, loss and gain of genetic loci concurred with tumor karyotypes. Several abnormal gene loci not apparent by cytogenetics were also identified. All except 11B indicated loss of CDKN2A (encodes p14 and p16), with concomitant loss of CDKN2B (encodes p15) in 11A, 17B, and 81A. All 6 cell lines showed gain of PIK3CA (encodes a PI3 kinase) located at 3q26.3.
Conclusions We provide evidence for the role of 3 critical pathways in the development and progression of HNSCC. The CDKN2A/B genes encode various components of the Rb and p53 pathways, and the PIK3CA gene makes a catalytic subunit of the protein phosphatidylinositol 3-OH kinase (PI3K), which is known to be involved in the PI3K/ATK signaling pathways. Molecular events may ultimately serve to achieve genomic alterations that set off an interplay among key gene loci along discrete genetic pathways used by tumor cells in HNSCC.
From the Research Division (Drs Worsham and Concus), Department of Otolaryngology–Head and Neck Surgery (Drs Concus and Benninger), Henry Ford Health System, Detroit, Mich; Department of Clinical Genetics, VU Medical Center, Amsterdam, the Netherlands (Drs Pals and van Spaendonk); Microbiology Research Center–Holland, Amsterdam (Dr Schouten); and Department of Otolaryngology–Head Neck Surgery, University of Michigan, Ann Arbor (Dr Carey). The authors have no relevant financial interest in this article.
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