metricas
covid
Buscar en
Cirugía Española
Toda la web
Inicio Cirugía Española Valor pronóstico de la pérdida de heterozigosidad en la región 9p21 en el car...
Información de la revista
Vol. 70. Núm. 1.
Páginas 6-12 (julio 2001)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 70. Núm. 1.
Páginas 6-12 (julio 2001)
Acceso a texto completo
Valor pronóstico de la pérdida de heterozigosidad en la región 9p21 en el carcinoma broncogénico no microcítico
Prognostic value of loss of heterozygosity at chromosome 9p21 in nonsmall cell bronchogenic carcinoma
Visitas
4457
M.T. Sanz-Casla1,*, M.L. Maestro*, A. Godino*, I. Zanna*, A. Torres**, J.L. Balibrea**
* Servicios de Análisis Clínicos
** Cirugía II. Hospital Clínico San Carlos. Madrid
Este artículo ha recibido
Información del artículo
Resumen
Bibliografía
Descargar PDF
Estadísticas
Resumen

La importancia sociosanitaria del cáncer de pulmón radica en su elevada incidencia y mortalidad. En la actualidad se considera el cáncer como el resultado de una acumulación de alteraciones que afectan a diversos genes con distintas funciones celulares. Diversos estudios genéticos han demostrado una pérdida de material genético en la región 21 del brazo corto del cromosoma 9 (9p21), siendo una de las alteraciones genéticas más frecuentemente identificadas en el cáncer humano. Esta región contiene un gen supresor llamado p16, que codifica las proteínas p16 y p19.

Se estudió una serie de 98 pacientes diagnosticados de carcinoma de pulmón no microcítico. Se analizó la pérdida de heterozigosidad (LOH) en 9p21 mediante el análisis de polimorfismos de microsatélites. El 23,5% de los pacientes presentaba LOH y/o inestabilidad en 9p21. Contrariamente a lo que se esperaba, los pacientes que no presentaban alteraciones genéticas en p16 tenían un riesgo relativo de fallecer 1,7 veces mayor (p = 0,1) que los que sí presentaban LOH y/o inestabilidad.

Palabras clave:
Pérdida de heterozigosidad
Cromosoma 9 p16
Cáncer de pulmón no microcítico

The social and public health importance of lung cancer lies in its very high incidence and mortality rate. Cancer is currently believed to be the result of a cumulative process of genetic alterations affecting different genes with diverse cellular functions. Genetic studies have shown loss of genetic material in region 21 of the short arm of chromosome 9 (9p21). This seems to be one of the commonest alterations identified in human cancer. This region contains a suppressor gene, p16, which codifies the p16 and p19 proteins.

We studied 98 spatients with non-small cell lung cancer. Loss of heterozygosity (LOH) in 9p21 was analyzed using trough satellite polymorphism. LOH and/or instability of 9p21 was found in 23.5% of patients. Contrary to what was expected, patients not showing genetic alterations in p16 had a relative risk of death approximately 1.7 times (p = 0.1) higher than those not presenting LOH and/or instability.

Key words:
Loss of heterozygosity
Chromosome 9p16
Non-small cell lung cancer
El Texto completo está disponible en PDF
Bibliografía
[1.]
Mina D, Higgins G, Glatstein E. En: DeVita V, editor. Cáncer. Principios y prácticas de oncología. Salvat, 14: 371-445
[2.]
J.L. Balibrea.
Tumores pulmonares.
pp. 1258-1280
[3.]
C.F. Mountain.
Revisions in the International System for Staging Lung Cancer.
Chest, 111 (1997), pp. 1710-1717
[4.]
E.H. Lipford, J.C. Eggleston, K.D. Lillemoe.
Prognostic factors y surgicelly resected limited stage non-small cell carcinoma of the lung.
Am J Sur Pathol, 8 (1984), pp. 357-362
[5.]
M.L. Maestro, R. Rodríguez, M.T. Sanz, A. Torres, J.L. Balibrea.
Cáncer de pulmón: hacia un nuevo concepto de marcador tumoral.
Cir Esp, 63 (1998), pp. 53-60
[6.]
J. Kern, A. Filderman.
Oncogenes and growth factors in human lung cancer.
Clin Chest Med, 14 (1993), pp. 31-41
[7.]
R. Salgia, A.T. Skarin.
Molecular abnormalities in lung cancer.
J Clin Oncol, 16 (1998), pp. 1207-1217
[8.]
S. De Vos, C.W. Miller, S. Takeuchi, Af. Gombart, S.K. Cho, H.P. Koeffler.
Alterations of CDKN2 (p16) in non-small cell lung cancer.
Gen Chrom Cancer, 14 (1995), pp. 164-170
[9.]
A. Kamb, N.A. Gruis, J. Weaver-Feldhaus, Q. Liu, K. Harsman, S.V. Tavtigian, et al.
A cell cycle regulator potentially involved in the genesis of many tumor types.
Science, 264 (1994), pp. 436-440
[10.]
M. Serrano, G.J. Hannon, D. Beach.
A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4.
Nature, 366 (1993), pp. 704-707
[11.]
W.H. Liggett, D. Sidrnsky.
Role of the p16 tumor supressor gene in cancer.
J Clin Oncol, 16 (1998), pp. 1197-1206
[12.]
T. Nobori, K. Miura, D.J. Wu, A. Lois, K. Takabayashi, D.A. Carson.
Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers.
Nature, 368 (1994), pp. 753-756
[13.]
C.J. Sherr.
Cancer cell cycles.
Science, 274 (1996), pp. 1672
[14.]
M. Serrano, H. Lee, L. Chin, C. Cordon-Cardó, D. Beach, R. DePinho.
Role of the INK4a locus in tumor supression and cell mortality.
Cell, 85 (1996), pp. 27-37
[15.]
P. Cairns, T.j. Polascik, Y. Eby, K. Tokino, J. Califano, A. Merlo, et al.
Frequency of homozygous deletion at p16/CDKN2 in primary human tumours.
Nature Genet, 11 (1995), pp. 210-212
[16.]
A. Okamoto, S.P. Hussain, K. Hagiwara, E.A. Spillare, Mr. Rusin, D.J. Demetrick, et al.
Mutations y the p16/INK4/MTS1, P15/MTS2 AND P18 genes in primary and metastatic lung cancer.
Cancer Res, 55 (1995), pp. 1448-1451
[17.]
WHO. Histological typing of tumors. (2.a Ed.
Am J Clin Pathol, 77 (1982), pp. 123-126
[18.]
C.F. Mountain.
The new international staging system for lung cancer.
Surg Clin NA, 67 (1987), pp. 925-935
[19.]
A. Merlo, E. Gabrielson, F. Askin, Sidransky.
Frequent loss of chromosome 9 in human primary non-small cell lung cancer.
Cancer Res, 54 (1994), pp. 640-642
[20.]
O. Washimi, M. Nagatake, H. Osada, R. Ueda, T. Koshikawa, T. Seki, et al.
In vivo occurrence of p16 (MTS1) and p15 (MTS2) alterations preferentially in non-small-cell lung cancers.
Cancer Res, 55 (1995), pp. 514-517
[21.]
G. Shapiro, C. Edwards, L. Kobzik, J. Godleski, W. Richards, D. Sugarbaker, et al.
Reciprocal Rb inactivation and p16INK4 expression in primary lung cancers and cell lines.
Cancer Res, 55 (1995), pp. 505-509
[22.]
S. Xiao, D. Li, J. Corson, J. Vijg, J. Fletcher.
Codeletion of p15 and p16 genes in primary non-small cell lung carcinoma.
Cancer Res, 55 (1995), pp. 2968-2971
[23.]
I. Kinoshita, H. Dosaka-Akita, T. Misina, K. Akie, M. Nishi, H. Hiroumi, et al.
Altered p16INK4 and retinoblastoma protein status in non-small cell lung cancer: potential synergistic effect with altered p53 protein on proliferative activity.
Cancer Res, 56 (1996), pp. 5557-5562
[24.]
R. Kratzke, T. Greatens, J. Rubins, M. Maddaus, D. Niewoehner, G. Niehans, et al.
Rb and p16INK4a expression in resected non-small cell lung tumors.
Cancer Res, 56 (1996), pp. 3415-3420
[25.]
A. Marchetti, F. Buttitta, S. Peelegrini, G. Bertacca, A. Chella, V. Carnicelli, et al.
Alterations of p16 (MTS1) in node-positive non-small cell lung carcinomas.
[26.]
D. Betticher, G. White, S. Vonlanthen, X. Liu, A. Kappeler, H. Altermatt, et al.
G1 control gene status is frequently altered in resectable nonsmall cell lung cancer.
Int J Cancer, 74 (1997), pp. 556-562
[27.]
V. Gorgoulis, P. Zacharatos, A. Kotsinas, T. Liloglou, A. Kyroudi, M. Veslemes, et al.
Alterations of the p16-pRb pathway and the chromosome locus 9p21-22 in non-small-cell lung carcinomas.
Am J Path, 153 (1998), pp. 1749-1765
[28.]
K.M. Fong, P.V. Zimmerman, P.J. Smith.
Microsatellite instability and other molecular abnormalities in non-small cell lung cancer.
Cancer Res, 55 (1995), pp. 28-30
[29.]
S. Ahrendt, J. Chow, L. Xu, S. Yang, C. Eisenberger, M. Esteller, et al.
Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer.
J Nat Can Inst, 91 (1999), pp. 332-339
[30.]
C. Huang, T. Taki, M. Higashiyama, N. Kohno, M. Miyake.
p16 protein expression is associated with a poor prognosis in squamous cell carcinoma of the lung.
Br J Cancer, 82 (2000), pp. 374-380
[31.]
F. Hommura, H. Dosaka-Akita, I. Kinoshita, T. Mishina, H. Hiroumi, S. Ogura, et al.
Predictive value of expression of p16INK4A, retinoblastoma and p53 proteins for the prognosis of non-small-cell lung cancers.
Br J Cancer, 81 (1999), pp. 696-701
[32.]
S. Taga, T. Osaki, A. Ohgami, H. Imoto, T. Yoshimatsu, I. Yoshino, et al.
Prognostic value of the immunohistochemical detection of p16INK4 expression in nonsmall cell lung carcinoma.
Cancer, 80 (1997), pp. 389-395
[33.]
J. Geradts, K. Fong, P. Zimmerman, R. Maynard, J. Minna.
Correlation of abnormal Rb, P16ink4a, and expression with 3p loss of heterozygosity, other genetic abnormalities, and clinical features in 103 primary non-small cell lung cancers.
Clin Can Res, 5 (1999), pp. 791-800
Copyright © 2001. Asociación Española de Cirujanos
Descargar PDF
Opciones de artículo
es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos