Delineating genetic pathways of disease progression in head and neck squamous cell carcinoma.
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.


METHODS
Individual gene loci were analyzed for genetic alterations using a novel genomewide strategy.


METHODS
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.
Worsham
Maria J
MJ
Department of Otolaryngology-Head and Neck Surgery, Research Division, Henry Ford Health System, Detroit, MI 48202, USA. mworsha1@hfhs.org
Pals
Gerard
G
Schouten
Jan P
JP
Van Spaendonk
Rosalind M L
RM
Concus
Adriane
A
Carey
Thomas E
TE
Benninger
Michael S
MS
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D019942:Genes, p16 / Q000502:physiology; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D015345:Oligonucleotide Probes; D019869:Phosphatidylinositol 3-Kinases; D014407:Tumor Cells, Cultured
D015345:Oligonucleotide Probes; D019869:Phosphatidylinositol 3-Kinases