RASSF1A methylation and K-ras and B-raf mutations and recurrent endometrial cancer

J. M A Pijnenborg, G. C. Dam-de Veen, N. Kisters, B. Delvoux, M. van Engeland, J. G. Herman, P. G. Groothuis

Research output: Contribution to journalArticle

Abstract

Background: Aberrations in mediators of Ras signaling may increase the risk of developing recurrent endometrial carcinoma. Patients and methods: Primary tumors of patients with (n = 44) and without (n = 44) recurrent stage I endometrioid endometrial carcinoma were compared regarding the presence of K-ras mutations (codons 12 and 13), B- raf mutations (V599), and RASSF1A gene promoter methylation. Results: K-ras mutations were present in 18% of the patients independent of recurrent disease. No B-raf mutations were found. RASSF1A methylation was demonstrated in 85% of endometrial carcinomas, independent of recurrence. The presence of K-ras mutations and RASSF1A promoter methylation were not related, either directly or inversely. Analysis in premenopausal endometrial carcinomas demonstrated K-ras mutations in 40%, no B-raf mutations, and RASSF1A promoter methylation in 70% of the cases. RASSF1A methylation was also observed in samples of cyclic (n = 14), hyperplastic (n = 8), and atrophic (n = 13) endometrial tissues in 21%, 50% and 38%, respectively. Conclusions: RASSF1A methylation was observed in a high frequency in endometrioid endometrial carcinoma whereas K-ras and B-raf mutations were observed in a low frequency. No association was observed with the development of recurrent disease. High-frequency RASSF1A methylation in premenopausal carcinomas and an increased frequency in endometrial hyperplasia indicate that this may be an early event in endometrial carcinogenesis.

Original languageEnglish (US)
Pages (from-to)491-497
Number of pages7
JournalAnnals of Oncology
Volume18
Issue number3
DOIs
StatePublished - Mar 2007

Fingerprint

Endometrial Neoplasms
Methylation
Mutation
Endometrioid Carcinoma
Endometrial Hyperplasia
Codon
Carcinogenesis
Carcinoma
Recurrence
Genes
Neoplasms

Keywords

  • B-raf
  • Endometrial carcinoma
  • K-ras
  • Mutation
  • RASSF1A

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Pijnenborg, J. M. A., Dam-de Veen, G. C., Kisters, N., Delvoux, B., van Engeland, M., Herman, J. G., & Groothuis, P. G. (2007). RASSF1A methylation and K-ras and B-raf mutations and recurrent endometrial cancer. Annals of Oncology, 18(3), 491-497. https://doi.org/10.1093/annonc/mdl455

RASSF1A methylation and K-ras and B-raf mutations and recurrent endometrial cancer. / Pijnenborg, J. M A; Dam-de Veen, G. C.; Kisters, N.; Delvoux, B.; van Engeland, M.; Herman, J. G.; Groothuis, P. G.

In: Annals of Oncology, Vol. 18, No. 3, 03.2007, p. 491-497.

Research output: Contribution to journalArticle

Pijnenborg, JMA, Dam-de Veen, GC, Kisters, N, Delvoux, B, van Engeland, M, Herman, JG & Groothuis, PG 2007, 'RASSF1A methylation and K-ras and B-raf mutations and recurrent endometrial cancer', Annals of Oncology, vol. 18, no. 3, pp. 491-497. https://doi.org/10.1093/annonc/mdl455
Pijnenborg JMA, Dam-de Veen GC, Kisters N, Delvoux B, van Engeland M, Herman JG et al. RASSF1A methylation and K-ras and B-raf mutations and recurrent endometrial cancer. Annals of Oncology. 2007 Mar;18(3):491-497. https://doi.org/10.1093/annonc/mdl455
Pijnenborg, J. M A ; Dam-de Veen, G. C. ; Kisters, N. ; Delvoux, B. ; van Engeland, M. ; Herman, J. G. ; Groothuis, P. G. / RASSF1A methylation and K-ras and B-raf mutations and recurrent endometrial cancer. In: Annals of Oncology. 2007 ; Vol. 18, No. 3. pp. 491-497.
@article{08345f4d5e674fa8a1778002ec86f594,
title = "RASSF1A methylation and K-ras and B-raf mutations and recurrent endometrial cancer",
abstract = "Background: Aberrations in mediators of Ras signaling may increase the risk of developing recurrent endometrial carcinoma. Patients and methods: Primary tumors of patients with (n = 44) and without (n = 44) recurrent stage I endometrioid endometrial carcinoma were compared regarding the presence of K-ras mutations (codons 12 and 13), B- raf mutations (V599), and RASSF1A gene promoter methylation. Results: K-ras mutations were present in 18{\%} of the patients independent of recurrent disease. No B-raf mutations were found. RASSF1A methylation was demonstrated in 85{\%} of endometrial carcinomas, independent of recurrence. The presence of K-ras mutations and RASSF1A promoter methylation were not related, either directly or inversely. Analysis in premenopausal endometrial carcinomas demonstrated K-ras mutations in 40{\%}, no B-raf mutations, and RASSF1A promoter methylation in 70{\%} of the cases. RASSF1A methylation was also observed in samples of cyclic (n = 14), hyperplastic (n = 8), and atrophic (n = 13) endometrial tissues in 21{\%}, 50{\%} and 38{\%}, respectively. Conclusions: RASSF1A methylation was observed in a high frequency in endometrioid endometrial carcinoma whereas K-ras and B-raf mutations were observed in a low frequency. No association was observed with the development of recurrent disease. High-frequency RASSF1A methylation in premenopausal carcinomas and an increased frequency in endometrial hyperplasia indicate that this may be an early event in endometrial carcinogenesis.",
keywords = "B-raf, Endometrial carcinoma, K-ras, Mutation, RASSF1A",
author = "Pijnenborg, {J. M A} and {Dam-de Veen}, {G. C.} and N. Kisters and B. Delvoux and {van Engeland}, M. and Herman, {J. G.} and Groothuis, {P. G.}",
year = "2007",
month = "3",
doi = "10.1093/annonc/mdl455",
language = "English (US)",
volume = "18",
pages = "491--497",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - RASSF1A methylation and K-ras and B-raf mutations and recurrent endometrial cancer

AU - Pijnenborg, J. M A

AU - Dam-de Veen, G. C.

AU - Kisters, N.

AU - Delvoux, B.

AU - van Engeland, M.

AU - Herman, J. G.

AU - Groothuis, P. G.

PY - 2007/3

Y1 - 2007/3

N2 - Background: Aberrations in mediators of Ras signaling may increase the risk of developing recurrent endometrial carcinoma. Patients and methods: Primary tumors of patients with (n = 44) and without (n = 44) recurrent stage I endometrioid endometrial carcinoma were compared regarding the presence of K-ras mutations (codons 12 and 13), B- raf mutations (V599), and RASSF1A gene promoter methylation. Results: K-ras mutations were present in 18% of the patients independent of recurrent disease. No B-raf mutations were found. RASSF1A methylation was demonstrated in 85% of endometrial carcinomas, independent of recurrence. The presence of K-ras mutations and RASSF1A promoter methylation were not related, either directly or inversely. Analysis in premenopausal endometrial carcinomas demonstrated K-ras mutations in 40%, no B-raf mutations, and RASSF1A promoter methylation in 70% of the cases. RASSF1A methylation was also observed in samples of cyclic (n = 14), hyperplastic (n = 8), and atrophic (n = 13) endometrial tissues in 21%, 50% and 38%, respectively. Conclusions: RASSF1A methylation was observed in a high frequency in endometrioid endometrial carcinoma whereas K-ras and B-raf mutations were observed in a low frequency. No association was observed with the development of recurrent disease. High-frequency RASSF1A methylation in premenopausal carcinomas and an increased frequency in endometrial hyperplasia indicate that this may be an early event in endometrial carcinogenesis.

AB - Background: Aberrations in mediators of Ras signaling may increase the risk of developing recurrent endometrial carcinoma. Patients and methods: Primary tumors of patients with (n = 44) and without (n = 44) recurrent stage I endometrioid endometrial carcinoma were compared regarding the presence of K-ras mutations (codons 12 and 13), B- raf mutations (V599), and RASSF1A gene promoter methylation. Results: K-ras mutations were present in 18% of the patients independent of recurrent disease. No B-raf mutations were found. RASSF1A methylation was demonstrated in 85% of endometrial carcinomas, independent of recurrence. The presence of K-ras mutations and RASSF1A promoter methylation were not related, either directly or inversely. Analysis in premenopausal endometrial carcinomas demonstrated K-ras mutations in 40%, no B-raf mutations, and RASSF1A promoter methylation in 70% of the cases. RASSF1A methylation was also observed in samples of cyclic (n = 14), hyperplastic (n = 8), and atrophic (n = 13) endometrial tissues in 21%, 50% and 38%, respectively. Conclusions: RASSF1A methylation was observed in a high frequency in endometrioid endometrial carcinoma whereas K-ras and B-raf mutations were observed in a low frequency. No association was observed with the development of recurrent disease. High-frequency RASSF1A methylation in premenopausal carcinomas and an increased frequency in endometrial hyperplasia indicate that this may be an early event in endometrial carcinogenesis.

KW - B-raf

KW - Endometrial carcinoma

KW - K-ras

KW - Mutation

KW - RASSF1A

UR - http://www.scopus.com/inward/record.url?scp=33847630443&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847630443&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdl455

DO - 10.1093/annonc/mdl455

M3 - Article

C2 - 17170014

AN - SCOPUS:33847630443

VL - 18

SP - 491

EP - 497

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 3

ER -