Methylation: A second hit in the two-hit hypothesis

This case illustrates that methylation of one BRCA1 allele may serve as the second hit in a patient with a diploid locus and missense mutation on the other allele.

BRCAJ; Methylation; Mutation; DNA silencing

[1] Knudson A.G. Jr.: "Mutation and cancer: statistical study of retinoblastoma". Proc. Natl. Acad. Sci USA, 1971, 68, 820.

[2] Geisler J.P., Hatterman-Zogg M.A., Rathe J.A., Buller R.E.: "BRCAI dysfunction is common in ovarian cancer". J. Natl Cancer Inst., 2002, 94, 61.

[3] Lallas T.A., Buekers T.E., Buller R.E.: "BRCAI mutations in familial ovarian cancer". Malec. Genet. Metab., 1999, 67, 357.

[4] Lallas T.A., Buller R.E.: "SSCP techniques in BRCAl analysis". Malec. Genet. Metab., 1998, 64, 173.

[5] Geisler J.P., Rathe J.A., Hatteman-Zogg M.A., Lallas T.A., Kirby P.. Buller R.E.: "Ovarian cancer BRCAI mutation detection: Protein Truncation Test (PTT) outperforms Single Strand Conformation Polymorphism Analysis (SSCP)". Hum. Mut., 2001, 18, 337.

[6] Hilton J.L., Geisler J.P., Rathe J.A., Hattermann-Zogg M.A., De Young B., Buller R.E.: "Inactivation of BRCAl and BRCA2 in ovarian cancer". J. Natl. Cancer Inst., 2002, 94, 1396.

[7] Geisler J.P., Sood A.K., Holmes R.J., Hatterman-Zogg M.A., Rathe J.A., Buller R.E.: "Mismatch repair gene expression defects contribute to microsatellite instability in ovarian cancer". Cancer, (in press) 2003.