Mutation analysis of 24 known cancer genes in the NCI-60 cell line set

Ogechi N. Ikediobi; Helen Davies; Graham Bignell; Sarah Edkins; Claire Stevens; Sarah O'Meara; Thomas Santarius; Tim Avis; Syd Barthorpe; Lisa Brakenbury; Gemma Buck; Adam Butler; Jody Clements; Jennifer Cole; Ed Dicks; Simon Forbes; Kristian Gray; Kelly Halliday; Rachel Harrison; Katy Hills; Jonathan Hinton; Chris Hunter; Andy Jenkinson; David Jones; Vivienne Kosmidou; Richard Lugg; Andrew Menzies; Tatiana Mironenko; Adrian Parker; Janet Perry; Keiran Raine; David Richardson; Rebecca Shepherd; Alex Small; Raffaella Smith; Helen Solomon; Philip Stephens; Jon Teague; Calli Tofts; Jennifer Varian; Tony Webb; Sofie West; Sara Widaa; Andy Yates; William Reinhold; John N. Weinstein; Michael R. Stratton; P. Andrew Futreal; Richard Wooster

doi:10.1158/1535-7163.MCT-06-0433

Mutation analysis of 24 known cancer genes in the NCI-60 cell line set

Ogechi N. Ikediobi, Helen Davies, Graham Bignell, Sarah Edkins, Claire Stevens, Sarah O'Meara, Thomas Santarius, Tim Avis, Syd Barthorpe, Lisa Brakenbury, Gemma Buck, Adam Butler, Jody Clements, Jennifer Cole, Ed Dicks, Simon Forbes, Kristian Gray, Kelly Halliday, Rachel Harrison, Katy HillsJonathan Hinton, Chris Hunter, Andy Jenkinson, David Jones, Vivienne Kosmidou, Richard Lugg, Andrew Menzies, Tatiana Mironenko, Adrian Parker, Janet Perry, Keiran Raine, David Richardson, Rebecca Shepherd, Alex Small, Raffaella Smith, Helen Solomon, Philip Stephens, Jon Teague, Calli Tofts, Jennifer Varian, Tony Webb, Sofie West, Sara Widaa, Andy Yates, William Reinhold, John N. Weinstein, Michael R. Stratton, P. Andrew Futreal, Richard Wooster

Research output: Contribution to journal › Article › peer-review

353 Scopus citations

Abstract

The panel of 60 human cancer cell lines (the NCI-60) assembled by the National Cancer Institute for anticancer drug discovery is a widely used resource. The NCI-60 has been characterized pharmacologically and at the molecular level more extensively than any other set of cell lines. However, no systematic mutation analysis of genes causally implicated in oncogenesis has been reported. This study reports the sequence analysis of 24 known cancer genes in the NCI-60 and an assessment of 4 of the 24 genes for homozygous deletions. One hundred thirty-seven oncogenic mutations were identified in 14 (APC, BRAF, CDKN2, CTNNB1, HRAS, KRAS, NRAS, SMAD4, PIK3CA, PTEN, RB1, STK11, TP53, and VHL) of the 24 genes. All lines have at least one mutation among the cancer genes examined, with most lines (73%) having more than one. Identification of those cancer genes mutated in the NCI-60, in combination with pharmacologic and molecular profiles of the cells, will allow for more informed interpretation of anticancer agent screening and will enhance the use of the NCI-60 cell lines for molecularly targeted screens.

Original language	English (US)
Pages (from-to)	2606-2612
Number of pages	7
Journal	Molecular cancer therapeutics
Volume	5
Issue number	11
DOIs	https://doi.org/10.1158/1535-7163.MCT-06-0433
State	Published - Nov 2006
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1158/1535-7163.MCT-06-0433

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Ikediobi, O. N., Davies, H., Bignell, G., Edkins, S., Stevens, C., O'Meara, S., Santarius, T., Avis, T., Barthorpe, S., Brakenbury, L., Buck, G., Butler, A., Clements, J., Cole, J., Dicks, E., Forbes, S., Gray, K., Halliday, K., Harrison, R., ... Wooster, R. (2006). Mutation analysis of 24 known cancer genes in the NCI-60 cell line set. Molecular cancer therapeutics, 5(11), 2606-2612. https://doi.org/10.1158/1535-7163.MCT-06-0433

Ikediobi, ON, Davies, H, Bignell, G, Edkins, S, Stevens, C, O'Meara, S, Santarius, T, Avis, T, Barthorpe, S, Brakenbury, L, Buck, G, Butler, A, Clements, J, Cole, J, Dicks, E, Forbes, S, Gray, K, Halliday, K, Harrison, R, Hills, K, Hinton, J, Hunter, C, Jenkinson, A, Jones, D, Kosmidou, V, Lugg, R, Menzies, A, Mironenko, T, Parker, A, Perry, J, Raine, K, Richardson, D, Shepherd, R, Small, A, Smith, R, Solomon, H, Stephens, P, Teague, J, Tofts, C, Varian, J, Webb, T, West, S, Widaa, S, Yates, A, Reinhold, W, Weinstein, JN, Stratton, MR, Futreal, PA & Wooster, R 2006, 'Mutation analysis of 24 known cancer genes in the NCI-60 cell line set', Molecular cancer therapeutics, vol. 5, no. 11, pp. 2606-2612. https://doi.org/10.1158/1535-7163.MCT-06-0433

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title = "Mutation analysis of 24 known cancer genes in the NCI-60 cell line set",

abstract = "The panel of 60 human cancer cell lines (the NCI-60) assembled by the National Cancer Institute for anticancer drug discovery is a widely used resource. The NCI-60 has been characterized pharmacologically and at the molecular level more extensively than any other set of cell lines. However, no systematic mutation analysis of genes causally implicated in oncogenesis has been reported. This study reports the sequence analysis of 24 known cancer genes in the NCI-60 and an assessment of 4 of the 24 genes for homozygous deletions. One hundred thirty-seven oncogenic mutations were identified in 14 (APC, BRAF, CDKN2, CTNNB1, HRAS, KRAS, NRAS, SMAD4, PIK3CA, PTEN, RB1, STK11, TP53, and VHL) of the 24 genes. All lines have at least one mutation among the cancer genes examined, with most lines (73%) having more than one. Identification of those cancer genes mutated in the NCI-60, in combination with pharmacologic and molecular profiles of the cells, will allow for more informed interpretation of anticancer agent screening and will enhance the use of the NCI-60 cell lines for molecularly targeted screens.",

author = "Ikediobi, {Ogechi N.} and Helen Davies and Graham Bignell and Sarah Edkins and Claire Stevens and Sarah O'Meara and Thomas Santarius and Tim Avis and Syd Barthorpe and Lisa Brakenbury and Gemma Buck and Adam Butler and Jody Clements and Jennifer Cole and Ed Dicks and Simon Forbes and Kristian Gray and Kelly Halliday and Rachel Harrison and Katy Hills and Jonathan Hinton and Chris Hunter and Andy Jenkinson and David Jones and Vivienne Kosmidou and Richard Lugg and Andrew Menzies and Tatiana Mironenko and Adrian Parker and Janet Perry and Keiran Raine and David Richardson and Rebecca Shepherd and Alex Small and Raffaella Smith and Helen Solomon and Philip Stephens and Jon Teague and Calli Tofts and Jennifer Varian and Tony Webb and Sofie West and Sara Widaa and Andy Yates and William Reinhold and Weinstein, {John N.} and Stratton, {Michael R.} and Futreal, {P. Andrew} and Richard Wooster",

year = "2006",

month = nov,

doi = "10.1158/1535-7163.MCT-06-0433",

language = "English (US)",

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AU - Ikediobi, Ogechi N.

AU - Davies, Helen

AU - Bignell, Graham

AU - Edkins, Sarah

AU - Stevens, Claire

AU - O'Meara, Sarah

AU - Santarius, Thomas

AU - Avis, Tim

AU - Barthorpe, Syd

AU - Brakenbury, Lisa

AU - Buck, Gemma

AU - Butler, Adam

AU - Clements, Jody

AU - Cole, Jennifer

AU - Dicks, Ed

AU - Forbes, Simon

AU - Gray, Kristian

AU - Halliday, Kelly

AU - Harrison, Rachel

AU - Hills, Katy

AU - Hinton, Jonathan

AU - Hunter, Chris

AU - Jenkinson, Andy

AU - Jones, David

AU - Kosmidou, Vivienne

AU - Lugg, Richard

AU - Menzies, Andrew

AU - Mironenko, Tatiana

AU - Parker, Adrian

AU - Perry, Janet

AU - Raine, Keiran

AU - Richardson, David

AU - Shepherd, Rebecca

AU - Small, Alex

AU - Smith, Raffaella

AU - Solomon, Helen

AU - Stephens, Philip

AU - Teague, Jon

AU - Tofts, Calli

AU - Varian, Jennifer

AU - Webb, Tony

AU - West, Sofie

AU - Widaa, Sara

AU - Yates, Andy

AU - Reinhold, William

AU - Weinstein, John N.

AU - Stratton, Michael R.

AU - Futreal, P. Andrew

AU - Wooster, Richard

PY - 2006/11

Y1 - 2006/11

N2 - The panel of 60 human cancer cell lines (the NCI-60) assembled by the National Cancer Institute for anticancer drug discovery is a widely used resource. The NCI-60 has been characterized pharmacologically and at the molecular level more extensively than any other set of cell lines. However, no systematic mutation analysis of genes causally implicated in oncogenesis has been reported. This study reports the sequence analysis of 24 known cancer genes in the NCI-60 and an assessment of 4 of the 24 genes for homozygous deletions. One hundred thirty-seven oncogenic mutations were identified in 14 (APC, BRAF, CDKN2, CTNNB1, HRAS, KRAS, NRAS, SMAD4, PIK3CA, PTEN, RB1, STK11, TP53, and VHL) of the 24 genes. All lines have at least one mutation among the cancer genes examined, with most lines (73%) having more than one. Identification of those cancer genes mutated in the NCI-60, in combination with pharmacologic and molecular profiles of the cells, will allow for more informed interpretation of anticancer agent screening and will enhance the use of the NCI-60 cell lines for molecularly targeted screens.

AB - The panel of 60 human cancer cell lines (the NCI-60) assembled by the National Cancer Institute for anticancer drug discovery is a widely used resource. The NCI-60 has been characterized pharmacologically and at the molecular level more extensively than any other set of cell lines. However, no systematic mutation analysis of genes causally implicated in oncogenesis has been reported. This study reports the sequence analysis of 24 known cancer genes in the NCI-60 and an assessment of 4 of the 24 genes for homozygous deletions. One hundred thirty-seven oncogenic mutations were identified in 14 (APC, BRAF, CDKN2, CTNNB1, HRAS, KRAS, NRAS, SMAD4, PIK3CA, PTEN, RB1, STK11, TP53, and VHL) of the 24 genes. All lines have at least one mutation among the cancer genes examined, with most lines (73%) having more than one. Identification of those cancer genes mutated in the NCI-60, in combination with pharmacologic and molecular profiles of the cells, will allow for more informed interpretation of anticancer agent screening and will enhance the use of the NCI-60 cell lines for molecularly targeted screens.

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Mutation analysis of 24 known cancer genes in the NCI-60 cell line set

Abstract

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