Abstract
Germline TP53 splicing mutations have been described infrequently (>2%) in the literature, however in a series of 40 patients and families identified by our group in which there are germline TP53 mutations, seven affect splicing (18%). The low figure reported in the literature might reflect the method of mutation detection, which in many studies does not include all splice junctions. These data indicate that a significant proportion of TP53 germline mutations are currently unrecognized. We have carried out detailed studies of the effects of the different mutations on splicing, and see distinct variations in the effects of the same mutation in different patients. Furthermore we have identified the usage of a non-consensus splice donor site in four families with an intron 4 splice donor mutation.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Bartek J, Bartkova J, Vojtesek B, Staskova Z, Lukas J, Rejthar A, Kovarik J, Midgley CA, Gannon JV, Lane DP . 1991 Oncogene 6: 1699–1703
Beroud C, Soussi T . 1998 Nucleic. Acids Res. 26: 200–204
Birch JM, Blair V, Kelsey AM, Evans DGR, Harris M, Tricker KJ, Varley JM . 1998 Oncogene 17: 1061–1068
Birch JM, Hartley AL, Tricker KJ, Prosser J, Condie A, Kelsey AM, Harris M, Morris Jones PH, Binchy A, Crowther D, Craft AW, Eden OB, Evans DGR, Thompson E, Mann JR, Martin J, Mitchell ELD, Santibanez-Koref MF . 1994a Cancer Res. 54: 1298–1304
Birch JM, Heighway J, Teare MD, Kelsey AM, Hartley AL, Tricker KJ, Crowther D, Lane DP, Santibanez-Koref MF . 1994b Br. J. Cancer 70: 1176–1181
Boyle JM, Greaves MJ, Camplejohn RS, Birch JM, Roberts SA, Varley JM . 1999 Br. J. Cancer 79: 1657–1664
Boyle JM, Mitchell ELD, Greaves MJ, Roberts SA, Tricker K, Burt E, Varley JM, Birch JM, Scott D . 1997 Br. J. Cancer 77: 2181–2192
Brugières L, Gardes M, Moutou C, Chompret A, Meresse V, Martin A, Poisson N, Flamant F, Bonaïti-Pellié C, Lemerle J, Feunteun J . 1993 Cancer Res. 53: 452–455
Casey G, Lopez ME, Ramos JC, Plummer SJ, Arboleda MJ, Shaughnessy M, Karlan B, Slamon DJ . 1996 Oncogene 13: 1971–1981
Chen S, Anderson K, Moore MJ . 2000 Proc. Natl. Acad. Sci. USA 97: 593–598
Felix CA, Strauss EA, D'Amico D, Tsokos M, Winter S, Mitsudomi T, Nau MM, Brown DL, Leahey AM, Horowitz ME, Poplack DG, Costin D, Minna JD . 1993 Oncogene 8: 1203–1210
Frebourg T, Barbier N, Yan Y, Garber JE, Dreyfus M, Fraumeni J, Li FP, Friend SH . 1995 Am. J. Hum. Genet. 56: 608–615
Hernandez-Boussard T, Rodriguez-Tome P, Montesano R, Hainault P . 1999 Hum. Mut. 14: 1–8
Jolly KW, Malkin D, Douglass EC, Brown TF, Sinclair AE, Look AT . 1994 Oncogene 9: 97–102
Li FP, Fraumeni JF . 1969 Annals of Internal Medicine 71: 747–752
Li FP, Fraumeni JF, Mulvihill JJ, Blattner WA, Dreyfus MG, Tucker MA, Miller RW . 1988 Cancer Res. 48: 5358–5362
Midgley CA, Fisher CJ, Bartek J, Vojtesek B, Lane D, Barnes DM . 1992 J. Cell Sci. 101: 183–189
Mount SM . 2000 Am. J. Hum. Genet. 67: 788–792
Sedlacek Z, Kodet R, Poustka A, Goetz P . 1998 Nucleic Acids Res. 26: 1214–1215
Shapiro MB, Senapathy P . 1987 Nucleic Acids Res. 15: 7155–7174
Varley JM, Chapman P, McGown G, Thorncroft M, White GRM, Greaves MJ, Scott D, Spreadborough A, Tricker KJ, Birch JM, Evans DGR, Reddel R, Camplejohn RS, Burn J, Boyle JM . 1998a Oncogene 16: 3291–3298
Varley JM, Evans DGR, Birch JM . 1997a Br. J. Cancer 76: 1–14
Varley JM, McGown G, Thorncroft M, Cochrane S, Morrison P, Woll P, Kelsey AM, Mitchell ELD, Boyle J, Birch JM, Evans DGR . 1996a Oncogene 12: 2437–2442
Varley JM, McGown G, Thorncroft M, James LA, Margison GP, Forster G, Evans DGR, Harris M, Kelsey AM, Birch JM . 1999 Am. J. Hum. Genet. 65: 995–1006
Varley JM, McGown G, Thorncroft M, Santibanez-Koref MF, Kelsey AM, Tricker KJ, Evans DGR, Birch JM . 1997b Cancer Res. 57: 3245–3252
Varley JM, McGown G, Thorncroft M, Tricker KJ, Teare MD, Santibanez-Koref MF, Houlston RS, Martin J, Birch JM, Evans DGR . 1995 J. Med. Genet. 32: 946–950
Varley JM, McGown G, Thorncroft M, White GRM, Tricker KJ, Birch JM, Evans DGR . 1998b Br. J. Cancer 78: 1081–1083
Varley JM, Thorncroft M, McGown G, Appleby J, Kelsey AM, Tricker KM, Evans DGR, Birch JM . 1997c Oncogene 14: 865–871
Varley JM, Thorncroft M, McGown G, Tricker K, Birch JM, Evans DGR . 1996b Cancer Genet. Cytogenet. 90: 14–16
Verselis SJ, Rheinwald JG, Fraumeni JF, Li FP . 2000 Oncogene 19: 4230–4235
Warneford SG, Witton LJ, Townsend ML, Rowe PB, Reddel RR, Dalla-Pozza L, Symonds G . 1992 Cell Growth Differ. 3: 839–846
Acknowledgements
We thank the Cancer Research Campaign for continued financial support and our many clinical colleagues for providing material and referring families to us.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Varley, J., Attwooll, C., White, G. et al. Characterization of germline TP53 splicing mutations and their genetic and functional analysis. Oncogene 20, 2647–2654 (2001). https://doi.org/10.1038/sj.onc.1204369
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1204369
Keywords
This article is cited by
-
TP53 germline mutations in the context of families with hereditary breast and ovarian cancer: a clinical challenge
Archives of Gynecology and Obstetrics (2021)
-
Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor
Familial Cancer (2011)
-
Polymorphism in exon 4 of TP53 gene associated to HPV 16 and 18 in Mexican women with cervical cancer
Medical Oncology (2011)
-
RNA polymerase III transcription can be derepressed by oncogenes or mutations that compromise p53 function in tumours and Li-Fraumeni syndrome
Oncogene (2002)
-
Assessing TP53 status in human tumours to evaluate clinical outcome
Nature Reviews Cancer (2001)