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Spotlight on Molecular Profiling

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 Brackenbury, 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 and Richard Wooster
Ogechi N. Ikediobi
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Helen Davies
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Sarah Edkins
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Claire Stevens
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Sarah O'Meara
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Thomas Santarius
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Tim Avis
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Lisa Brackenbury
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Gemma Buck
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Adam Butler
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Jennifer Cole
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Ed Dicks
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Simon Forbes
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Kristian Gray
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Katy Hills
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Rebecca Shepherd
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Alex Small
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DOI: 10.1158/1535-7163.MCT-06-0433 Published November 2006
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  • Table 1.

    NCI-60 cell lines

    Cell lineTumor type
    786-0renal cell carcinoma
    A498renal cell carcinoma
    A549lung carcinoma
    ACHNrenal cell carcinoma
    BT-549breast carcinoma
    CAKI-1renal cell carcinoma
    CCRF-CEMacute lymphoblastic leukaemia
    COLO205colorectal carcinoma
    DU-145prostate carcinoma
    EKVXlung adenocarcinoma
    HCC-2998colorectal carcinoma
    HCT-116colorectal carcinoma
    HCT-15colorectal carcinoma
    HL-60acute myeloid leukaemia
    HOP62lung adenocarcinoma
    HOP-92lung large cell carcinoma
    HS578Tbreast carcinoma
    HT29colorectal carcinoma
    IGROV1ovarian carcinoma
    K-562chronic myeloid leukaemia
    KM12colorectal carcinoma
    LOXIMVImelanoma
    M14melanoma
    MALME-3Mmelanoma
    MCF7breast carcinoma
    MDA-MB-231breast carcinoma
    MDA-MB-435melanoma (see text)
    MOLT-4acute lymphoblastic leukaemia
    NCI/ADR-RESovarian carcinoma (see text)
    NCI-H226lung squamous cell carcinoma
    NCI-H23lung adenocarcinoma
    NCI-H322Mlung bronchoalveolar carcinoma
    NCI-H460lung large cell carcinoma
    NCI-H522lung adenocarcinoma
    OVCAR3ovarian carcinoma
    OVCAR-4ovarian carcinoma
    OVCAR-5ovarian carcinoma
    OVCAR-8ovarian carcinoma
    PC-3prostate carcinoma
    RPMI-8226myeloma
    RXF393renal cell carcinoma
    SF-268glioma
    SF-295glioma
    SF-539glioma
    SK-MEL-2melanoma
    SK-MEL-28melanoma
    SK-MEL-5melanoma
    SK-OV-3ovarian carcinoma
    SN12Crenal cell carcinoma
    SNB19glioma (see text)
    SNB-75glioma
    SRnon Hodgkin lymphoma
    SW620colorectal carcinoma
    T47Dbreast carcinoma
    TK-10renal cell carcinoma
    U251glioma
    UACC-257melanoma
    UACC-62melanoma
    UO-31renal cell carcinoma
  • Table 2.

    Cancer genes analyzed

    Gene symbolGene nameNational Center for Biotechnology Information gene IDLikely oncogenic mutations*
    APCAdenomatous polyposis coli3248
    BRAFv-raf murine sarcoma viral oncogene homologue B167310
    BRCA1Familial breast/ovarian cancer gene 16720
    BRCA2Familial breast/ovarian cancer gene 26750
    CDKN2ACyclin-dependent kinase inhibitor 2A, p16102933
    CTNNB1Catenin (cadherin associated protein) β114991
    ERBB2v-erb-b2 erythroblastic leukemia viral oncogene homologue 220640
    HRASv-Ha-ras Harvey rat sarcoma viral oncogene homologue32651
    EGFREpidermal growth factor receptor19560
    FLT3fms-related tyrosine kinase 323220
    KITv-KIT Hardy-Zuckerman 4 feline sarcoma viral oncogene homologue38150
    KRASv-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue384511
    MAP2K4Mitogen-activated protein kinase kinase 464160
    METmet proto-oncogene42330
    NRASNeuroblastoma RAS viral (v-ras) oncogene homologue48933
    PDGFRAPlatelet-derived growth factor receptor, α polypeptide51560
    PIK3CAPhosphoinositide-3-kinase, catalytic, α polypeptide52907
    PTENPhosphatase and tensin homologue572811
    RB1Retinoblastoma 159253
    RETret proto-oncogene59790
    SMAD4SMAD, mothers against DPP homologue 4 (MADH4)40892
    STK11Serine/threonine kinase 11/LKB1 (Peutz-Jehgers syndrome)67944
    TP53Tumor protein p53 (Li-Fraumeni syndrome)715741
    VHLvon Hippel-Lindau tumor suppressor74282
    • ↵* Mutations seen in common ancestor lines counted once.

  • Table 3.

    Mutations/variants identified in 24 cancer genes in the NCI-60

    Cell lineVariants identified
    786-0CDKN2A Hom c.1_150 del 150, p.? LOM; PTEN Hom c.445C>T, p.Q149X LOM; TP53 Het c.832C>G, P278A c.A560-2A>G, p.? LOM; VHL Hom c.311delG p.G105fsX55 LOM
    A498CDKN2A Hom c.1_471 del 471, p.? LOM; VHL Hom c.426_429delTGAC p.G144fsX14 LOM
    A549CDKN2A Hom c.1_471 del 471, p.? LOM; KRAS Hom c.34G>A, p.G12S LOM; STK11 Hom c.109C>T, p.Q37X LOM
    ACHNCDKN2A Hom c.1_471 del 471, p.? LOM
    BT-549RB1 Hom c.265_607 del 343, p.? LOM; TP53 Hom c.747G>C, p.R249S LOM
    CAKI-1CDKN2A Hom c.1_471 del 471, p.? LOM
    CCRF-CEMCDKN2A Hom c.1_471 del 471, p.? LOM; KRAS Het c.35G>A, p.G12D LOM; PTEN Hom c. del 80-492, p.? LOM; TP53 Het c.743G>A, p.R248Q c.524G>A, p.R175H LOM; FLT3 Het c.1879G>A p.A627T TOV
    COLO-205APC Hom c.4666_4667insA p.T1556fsX3 LOM; BRAF Het c.1799T>A, p.V600E LOM; SMAD4 Hom del exon1-6 LOM; TP53 Hom c.308_333>TA, p.Y103fsX37 LOM
    DU145CDKN2A Hom c.250G>T p.D84Y LOM; RB1 Hom c.2143A>T, p.K715X LOM; STK11 Hom c.532_536delAAGCC p.K178fsX86 LOM; TP53 Het c.820G>T, p.V274F LOM
    EKVXTP53 Hom c.609_610GG>TT, p.E204X LOM
    HCC2998APC Het c.1994T>A, p.L665X c.4348C>T, R1450X LOM; RB1 Het c.409G>T, p.E137X TOV; TP53 Het c.637C>T, p.R213X TOV
    HCT-116CDKN2A Het c.68_69insG p.R24fsX20 c.220delG p.E74fsX15 (p14) LOM; CTNNB1 c.133_135 del TCT, p.S45 del LOM; KRAS Het c.38G>A, p.G13D LOM; PIK3CA Het c.3140A>G, p.H1047R LOM; BRCA2 Het c.8021_8022insA p.I2675fsX6 TOV
    HCT-15APC Het c.6496C>T,p.R2166X Hom c.4248delC p.I1417fsX2 LOM; KRAS Het c.38G>A, p.G13D LOM; PIK3CA Het c. 1633G>A p. E545K LOM; TP53 Het c.C1101-2A>C, p.? C722T, S241F LOM; BRCA2 Het c.3599_3600delGT p.C1200fsX1 c.5351delA p.N1784fsX7 TOV
    HL-60CDKN2A Hom c.238C>T p.R80X LOM; NRAS Het c.182A>T, p.Q61L LOM; TP53 Hom deletion LOM
    HOP62CDKN2A Hom c.1_471 del 471, p.? LOM; KRAS Het c.34G>T, p.G12C LOM; TP53 Hom c.G673-2A>G, p.? LOM
    HOP-92CDKN2A Hom c.1_471 del 471, p.? LOM; TP53 Hom c.524G>T, p.R175L LOM
    Hs-578-TCDKN2A Hom c.1_471 del 471, p.? LOM; HRAS Het c.35G>A p.G12D LOM; TP53 Hom c.469G>T, p.V157F LOM
    HT-29APC Het c.2557G>T p.E853X c.4666_4667insA p.T1556fsX3 LOM; BRAF Het c.1799T>A, p.V600E LOM; SMAD4 Hom c.931C>T, p.Q311X LOM; PIK3CA Het c.1345C>A p.P449T LOM; TP53 Hom c.818G>A, p.R273H LOM
    IGROV-1TP53 Het c.377A>G, p.Y126C LOM; BRCA1 Het c.1961delA p.K654fsX47 TOV; SMAD4 Het c.692delG p.G231fsX10 TOV; PTEN Het c.955_958delACTT p.T319fsX1 TOV
    K-562CDKN2A Hom c.1_471 del 471, p.? LOM; TP53 Hom c.406_407insC p.Q136fsX13 LOM; PDGFRA Het Exon 10 +1 G>A p.? TOV
    KM12PTEN Het c.385G>T, p.G129X c.800 del A, p.K267fsX9 LOM; APC Het c.5454_5455 ins A, p.N1819fsX7 TOV; TP53 Het c.215delG, p.R72fsX51 TOV; BRCA2 Het c.5351delA p.N1784fsX7 TOV
    LOXIMVIBRAF Het c.1799T>A, p.V600E LOM; CDKN2A Hom c.1_471 del 471, p.? LOM
    M14/MDA-MB-435BRAF Het c.1799T>A, p.V600E LOM; CDKN2A Het c.150+2 T>C p.? c. 456-+24 AGgtgaggactgatgatctgagaattt >C p.? LOM; TP53 Het c.797G>A, p.G266E LOM
    MALME-3MBRAF Het c.1799T>A, p.V600E LOM; CDKN2A Hom c.1_471 del 471, p.? LOM
    MCF7CDKN2A Hom c.1_471 del 471, p.? LOM; PIK3CA Het c.1633G>A p.E545K LOM
    MDA-MB-231BRAF Het c.1391G>T, p.G464V LOM; CDKN2A Hom c.1_471 del 471, p.? LOM; KRAS Het c.38G>A p.G13D LOM; TP53 Hom c.839G>A, p.R280K LOM
    MOLT-4CDKN2A Hom c.1_471 del 471, p.? LOM; NRAS Het c.34G>T p.G12C LOM; PTEN Hom c.800delA p.K267fsX9 LOM; STK11 Het c.640C>T p.Q214X TOV; TP53 Het c.916C>T, p.R306X TOV
    NCI-H226CDKN2A Hom c.1_150 del 150, p.? LOM
    NCI-H23KRAS Het c.34G>T, p.G12C LOM; STK11 Hom c.996G>A, p.W332X LOM; TP53 Hom c.738G>C, p.M246I LOM
    NCI-H322MTP53 Hom c.743G>T, p.R248L LOM
    NCI-H460CDKN2A Hom del 1_457 del 457, p.? LOM; KRAS Hom c.183A>T, p.Q61H LOM; PIK3CA Het c.1633G>A p.E545K LOM; STK11 Hom c.109C>T p. Q37X LOM
    NCI-H522TP53 Hom 572delC, p.P191fsX56 LOM
    OVCAR-3TP53 Hom c.743G>A, p.R248Q LOM
    OVCAR-4TP53 Hom c.388C>G, p.L130V LOM
    OVCAR-5CDKN2A Hom c.1_471 del 471, p.? LOM; KRAS Hom c.35G>T, p.G12V LOM
    OVCAR-8/NCI/ADR-RESTP53 Hom c.376-1G>A, p.? LOM; ERBB2 Het c.2327G>T p.G776V TOV
    PC-3PTEN Hom c.165-1026 del 862, p.? LOM; TP53 Hom c.414delC p.K139fsX31 LOM
    RPMI-8226KRAS Het c.35G>C, p.G12A LOM; TP53 Hom c.853G>A, p.E285K LOM; EGFR Het c.2252C>T p.T751I TOV
    RXF393CDKN2A Hom c.1_471 del 471, p.? LOM; PTEN Hom c.1_164 del 164, p.? LOM; TP53 Hom c.524G>A, p.R175H LOM
    SF-268CDKN2A Hom c.1_471 del 471, p.? LOM; TP53 Hom c.818G>A, p.R273H LOM
    SF-295CDKN2A Hom c.1_471 del 471, p.? LOM; PTEN Hom c.697C>T, p.R233X LOM; TP53 Hom c.743G>A, p.R248Q LOM
    SF539RB1 Hom c.346_349delACTT p.T116fsX8 LOM; TP53 Hom c.1024delC p.R342fsX3 LOM; PTEN Hom c.1-1026 del 1026, p.? LOM
    SK-MEL-2NRAS Hom c.182A>G, p.Q61R LOM; TP53 Het c.733G>A, p.G245S LOM
    SK-MEL-28BRAF Hom c.1799T>A, p.V600E LOM; TP53 Hom c.435_436G>GT, p.L145R LOM; EGFR Hom c.2257C>T p.P753S TOV
    SK-MEL-5BRAF Het c.1799T>A, p.V600E LOM; CDKN2A Hom c.1_471 del 471, p.? LOM
    SK-OV-3CDKN2A Hom del 1_457 del 457, p.? LOM; PIK3CA Het c.3140A>G, p.H1047R LOM; TP53 Hom c. del267C p.S90fsX33 LOM; APC Het c.4666delA p.T1556fsX9 TOV
    SN12CTP53 Hom c.1006G>T, p.E336X LOM
    SNB-75TP53 Hom c.772G>A, p.E258K LOM
    SRCDKN2A Hom c.1_471 del 471, p.? LOM
    SW620KRAS Hom c.35G>T, p.G12V LOM; TP53 Hom c.818G>A, p.R273H C925T, p.P309S LOM; APC Hom c.4012C>T, p.Q1338X LOM
    T47DPIK3CA Het c.3140A>G, p.H1047R LOM; TP53 Hom c.580C>T, p.L194F LOM
    TK10TP53 Het c.791T>G, p.L264R LOM
    U251/SNB-19CDKN2A Hom c.1_471 del 471, p.? LOM; PTEN Hom c.723_724insTT p.E242fsX15 LOM; TP53 Hom c.818G>A, p.R273H LOM
    UACC-257BRAF Het c.1799T>A, p.V600E LOM
    UACC-62BRAF Hom c.1799T>A, p.V600E LOM; CDKN2A Hom c.1_471 del 471, p.? LOM; PTEN Hom c.741_742insA p.P248fsX5 LOM
    UO-31CDKN2A Hom c.1_471 del 471, p.? LOM
    • Abbreviations: Hom, homozygous; Het, heterozygous; del, deletion; ins, insertion; LOM, likely oncogenic mutation; TOV, tentative oncogenic variant.

Additional Files

  • Tables
  • Supplementary Material, Ikediobi

    Files in this Data Supplement:

    • Supplementary Table S1
    • Supplementary Table S2
    • Supplementary Table S3
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Molecular Cancer Therapeutics: 5 (11)
November 2006
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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 Brackenbury, 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 and Richard Wooster
Mol Cancer Ther November 1 2006 (5) (11) 2606-2612; DOI: 10.1158/1535-7163.MCT-06-0433

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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 Brackenbury, 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 and Richard Wooster
Mol Cancer Ther November 1 2006 (5) (11) 2606-2612; DOI: 10.1158/1535-7163.MCT-06-0433
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Copyright © 2019 by the American Association for Cancer Research.

Molecular Cancer Therapeutics
eISSN: 1538-8514
ISSN: 1535-7163

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