Un nuevo estudio ha revelado marcadas diferencias en el terreno genómica de los dos tipos más comunes de cáncer de cuello uterino, lo que sugiere que los pacientes que podrían beneficiarse de terapias moleculares dirigidas a la idiosincrasia de cada tipo.
El estudio, publicado el 23 de agosto 2013 en la versión online de la revista Cancer realizado por investigadores del Instituto del Cáncer Dana-Farber y el Hospital Brigham y de Mujeres (BWH), es el primero en comparar el espectro de mutaciones genéticas relacionadas con el cáncer en los dos principales subtipos de cáncer de cuello uterino - adenocarcinoma y carcinoma de células escamosas. En pruebas con 80 muestras de tumores de cuello uterino, los investigadores encontraron altas tasas de mutaciones en dos genes: PIK3CA y KRAS. Aunque las mutaciones PIK3CA aparecieron en ambos subtipos, se encontraron mutaciones de KRAS sólo en adenocarcinomas.
Oncogenic mutations in cervical cancer
Wright, A. A., Howitt, B. E., Myers, A. P., Dahlberg, S. E., Palescandolo, E., Van Hummelen, P., MacConaill, L. E., Shoni, M., Wagle, N., Jones, R. T., Quick, C. M., Laury, A., Katz, I. T., Hahn, W. C., Matulonis, U. A. and Hirsch, M. S.
BACKGROUND: Cervical cancer is the second leading cause of cancer deaths among women worldwide. The objective of this study was to describe the most common oncogenic mutations in cervical cancers and to explore genomic differences between the 2 most common histologic subtypes: adenocarcinoma and squamous cell carcinoma. METHODS: A high-throughput genotyping platform, termed Oncomap, was used to interrogate 80 cervical tumors for 1250 known mutations in 139 cancer genes. Samples were analyzed using a mass spectrometry-based genotyping platform and were validated using orthogonal chemistry. Epidermal growth factor receptor (EGFR) mutations were further validated by massive parallel sequencing. Human papilloma virus (HPV) genotyping also was performed. RESULTS: Validated mutations were detected in 48 of 80 tumors (60%) examined. The highest mutation rates were in the genes phosphatidylinositol 3-kinase, catalytic subunit α (PIK3CA) (31.3%); Kirsten rat sarcoma viral oncogene homolog (KRAS) (8.8%); and EGFR (3.8%). PIK3CA mutation rates did not differ significantly between adenocarcinomas and squamous cell carcinomas (25% vs 37.5%, respectively; P = .33). In contrast, KRAS mutations were identified only in adenocarcinomas (17.5% vs 0%; P = .01), and a novel EGFR mutation was detected only in squamous cell carcinomas (0% vs 7.5%; P = .24). There were no associations between HPV-16 or HPV-18 and somatic mutations or overall survival. In adjusted analyses, PIK3CA mutations were associated with shorter survival (67.1 months vs 90.3 months; hazard ratio, 9.1; 95% confidence interval, 2.8-29.5 months; P < .001). CONCLUSIONS: Cervical cancers harbor high rates of potentially targetable oncogenic mutations. In addition, cervical squamous cell carcinoma and adenocarcinoma have distinct molecular profiles, suggesting that clinical outcomes may be improved with the use of more tailored treatment strategies, including PI3K and MEK inhibitors. Cancer 2013. © 2013 American Cancer Society.