Investigation of methylation CpG islands in p16 and p15 genes in cutenaous and uveal malignant melanoma

locus 9p21 wystêpuj1 w wielu typach nowotworów, obejmuj1c równie¿ czerniaka z3oœliwego. W tym obszarze zlokalizowane s1 2 geny supresorowe: p16 (CDKN2A) i p15 (CDKN2B). Zmiany ekspresji tych genów mog1 byæ spowodowane przez: homozygotyczne i heterozygotyczne delecje, mutacje punktowe lub metylacjê odcinków promotorowych. W Zak3adzie Diagnostyki i Immunologii Nowotworów analizowano 110 przypadków czerniaka z3oœliwego skóry i ga3ki ocznej. W ¿adnym z przypadków nie wykryto metylacji wysp CpG w genach p16 i p15. Wydaje siê zatem, ¿e proces metylacji wysp CpG w odcinkach promotorowych nie jest g3ównym mechanizmem wyciszania ekspresji obu genów w czerniaku z3oœliwym skóry i ga3ki ocznej.

[1]  J. Herman,et al.  p15(INK4B) CpG island methylation in primary acute leukemia is heterogeneous and suggests density as a critical factor for transcriptional silencing. , 1999, Blood.

[2]  R. Dahse,et al.  Analysis of the tumor suppressor gene p16(INK4A) in microdissected melanoma metastases by sequencing, and microsatellite and methylation screening , 1999, Archives of Dermatological Research.

[3]  M. Takata,et al.  p16INK4a inactivation is not frequent in uncultured sporadic primary cutaneous melanoma , 1999, Oncogene.

[4]  D. Sidransky,et al.  Analysis of p16 (CDKN2/MTS-1/INK4A) alterations in primary sporadic uveal melanoma. , 1999, Investigative ophthalmology & visual science.

[5]  D. Wong,et al.  p16INK4a expression is frequently decreased and associated with 9p21 loss of heterozygosity in sporadic melanoma , 1998, Journal of cutaneous pathology.

[6]  Y. Matsumura,et al.  Mutations of p16 and p15 tumor suppressor genes and replication errors contribute independently to the pathogenesis of sporadic malignant melanoma , 1998, Archives of Dermatological Research.

[7]  Yue Xiong,et al.  ARF Promotes MDM2 Degradation and Stabilizes p53: ARF-INK4a Locus Deletion Impairs Both the Rb and p53 Tumor Suppression Pathways , 1998, Cell.

[8]  H. Serizawa.  Cyclin-dependent Kinase Inhibitor p16INK4A Inhibits Phosphorylation of RNA Polymerase II by General Transcription Factor TFIIH* , 1998, The Journal of Biological Chemistry.

[9]  D. Sidransky,et al.  Role of the p16 tumor suppressor gene in cancer. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  M. Landthaler,et al.  p16INK4A/MTS1/CDKN2 – das „Melanomgen”? Stand der Forschung und Ausblick , 1998, Der Hautarzt.

[11]  Goos,et al.  Homozygous deletion of the p16INK4a and the p15INK4b tumour suppressor genes in a subset of human sporadic cutaneous malignant melanoma , 1998, The British journal of dermatology.

[12]  N. Hayward,et al.  Low frequency of p16/CDKN2A methylation in sporadic melanoma: comparative approaches for methylation analysis of primary tumors. , 1997, Cancer research.

[13]  M. Ng,et al.  Frequent hypermethylation of p16 and p15 genes in multiple myeloma. , 1997, Blood.

[14]  Ashutosh Kumar Singh,et al.  Genetic aspects of uveal melanoma: a brief review. , 1996, Seminars in oncology.

[15]  J. Herman,et al.  Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[16]  N. Bornfeld,et al.  Prognostic implications of monosomy 3 in uveal melanoma , 1996, The Lancet.

[17]  C. Shields,et al.  Deletion mapping of chromosome region 9p21‐p22 surrounding the CDKN2 locus in melanoma , 1996, International journal of cancer.

[18]  J. Herman,et al.  Hypermethylation-associated inactivation indicates a tumor suppressor role for p15INK4B. , 1996, Cancer research.

[19]  M. Inganäs,et al.  Mutational analysis of the CDKN2 gene in metastases from patients with cutaneous malignant melanoma. , 1996, British Journal of Cancer.

[20]  Kathleen R. Cho,et al.  Frequency of homozygous deletion at p16/CDKN2 in primary human tumours , 1995, Nature Genetics.

[21]  H. Koeffler,et al.  Role of the cyclin-dependent kinase inhibitors in the development of cancer. , 1995, Blood.

[22]  J. Herman,et al.  5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers , 1995, Nature Medicine.

[23]  Gregory J. Hannon,et al.  pl5INK4B is a potentia| effector of TGF-β-induced cell cycle arrest , 1994, Nature.

[24]  G. Hannon,et al.  A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4 , 1993, Nature.

[25]  R. Macsween.  Pathobiology of Ocular Disease: A Dynamic Approach , 1983 .