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Activating K-Ras mutations outwith 'hotspot' codons in sporadic colorectal tumours

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Activating K-Ras mutations outwith 'hotspot' codons in sporadic colorectal tumours : implications for personalised cancer medicine. / Smith, G.; Bounds, R.; Wolf, H.; Steele, Robert; Carey, Francis; Wolf, Roland (Lead / Corresponding author).

In: British Journal of Cancer, Vol. 102, No. 4, 16.02.2010, p. 693-703.

Research output: Contribution to journalArticle

Harvard

Smith, G, Bounds, R, Wolf, H, Steele, R, Carey, F & Wolf, R 2010, 'Activating K-Ras mutations outwith 'hotspot' codons in sporadic colorectal tumours: implications for personalised cancer medicine' British Journal of Cancer, vol 102, no. 4, pp. 693-703., 10.1038/sj.bjc.6605534

APA

Smith, G., Bounds, R., Wolf, H., Steele, R., Carey, F., & Wolf, R. (2010). Activating K-Ras mutations outwith 'hotspot' codons in sporadic colorectal tumours: implications for personalised cancer medicine. British Journal of Cancer, 102(4), 693-703. 10.1038/sj.bjc.6605534

Vancouver

Smith G, Bounds R, Wolf H, Steele R, Carey F, Wolf R. Activating K-Ras mutations outwith 'hotspot' codons in sporadic colorectal tumours: implications for personalised cancer medicine. British Journal of Cancer. 2010 Feb 16;102(4):693-703. Available from: 10.1038/sj.bjc.6605534

Author

Smith, G.; Bounds, R.; Wolf, H.; Steele, Robert; Carey, Francis; Wolf, Roland (Lead / Corresponding author) / Activating K-Ras mutations outwith 'hotspot' codons in sporadic colorectal tumours : implications for personalised cancer medicine.

In: British Journal of Cancer, Vol. 102, No. 4, 16.02.2010, p. 693-703.

Research output: Contribution to journalArticle

Bibtex - Download

@article{48784e988cdc4341b1e996c3df862db3,
title = "Activating K-Ras mutations outwith 'hotspot' codons in sporadic colorectal tumours: implications for personalised cancer medicine",
keywords = "K-Ras, mutation, colorectal tumour, Gene amplification, Personalised medicine, Signalling pathway, Costello syndrome, Point mutation, Colon cancer, Kirsten Ras, B-Raf, Cetuximab, Cells, Gene",
author = "G. Smith and R. Bounds and H. Wolf and Robert Steele and Francis Carey and Roland Wolf",
year = "2010",
doi = "10.1038/sj.bjc.6605534",
volume = "102",
number = "4",
pages = "693--703",
journal = "British Journal of Cancer",
issn = "0007-0920",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Activating K-Ras mutations outwith 'hotspot' codons in sporadic colorectal tumours

T2 - implications for personalised cancer medicine

A1 - Smith,G.

A1 - Bounds,R.

A1 - Wolf,H.

A1 - Steele,Robert

A1 - Carey,Francis

A1 - Wolf,Roland

AU - Smith,G.

AU - Bounds,R.

AU - Wolf,H.

AU - Steele,Robert

AU - Carey,Francis

AU - Wolf,Roland

PY - 2010/2/16

Y1 - 2010/2/16

N2 - <p>BACKGROUND: Response to EGFR-targeted therapies in colorectal cancer patients has been convincingly associated with Kirsten-Ras (K-Ras) mutation status. Current mandatory mutation testing for patient selection is limited to the K-Ras 'hotspot' codons 12 and 13.</p><p>METHODS: Colorectal tumours (n = 106) were screened for additional K-Ras mutations, phenotypes compared in transformation and Ras GTPase activating assays and gene and pathway changes induced by individual K-Ras mutants identified by microarray analysis. Taqman-based gene copy number and FISH analyses were used to investigate K-Ras gene amplification.</p><p>RESULTS: Four additional K-Ras mutations (Leu(19)Phe (1 out of 106 tumours), Lys(117)Asn (1 out of 106), Ala(146)Thr (7 out of 106) and Arg(164)Gln (1 out of 106)) were identified. Lys(117)Asn and Ala(146)Thr had phenotypes similar to the hotspot mutations, whereas Leu(19)Phe had an attenuated phenotype and the Arg(164)Gln mutation was phenotypically equivalent to wt K-Ras. We additionally identified a new K-Ras gene amplification event, present in approximately 2% of tumours.</p><p>CONCLUSIONS: The identification of mutations outwith previously described hotspot codons increases the K-Ras mutation burden in colorectal tumours by one-third. Future mutation screening to facilitate optimal patient selection for treatment with EGFR-targeted therapies should therefore be extended to codon 146, and in addition should consider the unique molecular signatures associated with individual K-Ras mutations. British Journal of Cancer (2010) 102, 693-703. doi:10.1038/sj.bjc.6605534 www.bjcancer.com (C) 2010 Cancer Research UK</p>

AB - <p>BACKGROUND: Response to EGFR-targeted therapies in colorectal cancer patients has been convincingly associated with Kirsten-Ras (K-Ras) mutation status. Current mandatory mutation testing for patient selection is limited to the K-Ras 'hotspot' codons 12 and 13.</p><p>METHODS: Colorectal tumours (n = 106) were screened for additional K-Ras mutations, phenotypes compared in transformation and Ras GTPase activating assays and gene and pathway changes induced by individual K-Ras mutants identified by microarray analysis. Taqman-based gene copy number and FISH analyses were used to investigate K-Ras gene amplification.</p><p>RESULTS: Four additional K-Ras mutations (Leu(19)Phe (1 out of 106 tumours), Lys(117)Asn (1 out of 106), Ala(146)Thr (7 out of 106) and Arg(164)Gln (1 out of 106)) were identified. Lys(117)Asn and Ala(146)Thr had phenotypes similar to the hotspot mutations, whereas Leu(19)Phe had an attenuated phenotype and the Arg(164)Gln mutation was phenotypically equivalent to wt K-Ras. We additionally identified a new K-Ras gene amplification event, present in approximately 2% of tumours.</p><p>CONCLUSIONS: The identification of mutations outwith previously described hotspot codons increases the K-Ras mutation burden in colorectal tumours by one-third. Future mutation screening to facilitate optimal patient selection for treatment with EGFR-targeted therapies should therefore be extended to codon 146, and in addition should consider the unique molecular signatures associated with individual K-Ras mutations. British Journal of Cancer (2010) 102, 693-703. doi:10.1038/sj.bjc.6605534 www.bjcancer.com (C) 2010 Cancer Research UK</p>

KW - K-Ras

KW - mutation

KW - colorectal tumour

KW - Gene amplification

KW - Personalised medicine

KW - Signalling pathway

KW - Costello syndrome

KW - Point mutation

KW - Colon cancer

KW - Kirsten Ras

KW - B-Raf

KW - Cetuximab

KW - Cells

KW - Gene

UR - http://www.scopus.com/inward/record.url?scp=76949093606&partnerID=8YFLogxK

U2 - 10.1038/sj.bjc.6605534

DO - 10.1038/sj.bjc.6605534

M1 - Article

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 4

VL - 102

SP - 693

EP - 703

ER -

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