A robust genomic signature for the detection of colorectal
cancer patients with microsatellite instability phenotype and
high mutation frequency

J 2012

A robust genomic signature for the detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequency

TIAN, Sun; Paul ROEPMAN; Vlad POPOVICI; Magali MICHAUT; Ian MAJEWSKI et al.

Základní údaje

Originální název

A robust genomic signature for the detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequency

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Vydání

JOURNAL OF PATHOLOGY, HOBOKEN, WILEY-BLACKWELL, 2012, 0022-3417

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 7.585

Označené pro přenos do RIV

DOI

https://doi.org/10.1002/path.4092

UT WoS

000313949800016

Klíčová slova anglicky

Colorectal cancer; microsatellite instability; deficient mismatch repair system; gene expression; mutation frequency; genomic signature; prognosis

Změněno: 4. 3. 2013 14:59, doc. Ing. Vlad Popovici, PhD

Anotace

V originále

Microsatellite instability (MSI) occurs in 10-20% of colorectal tumours and is associated with good prognosis. Here we describe the development and validation of a genomic signature that identifies colorectal cancer patients with MSI caused by DNA mismatch repair deficiency with high accuracy. Microsatellite status for 276 stage II and III colorectal tumours has been determined. Full-genome expression data was used to identify genes that correlate with MSI status. A subset of these samples (n = 73) had sequencing data for 615 genes available. An MSI gene signature of 64 genes was developed and validated in two independent validation sets: the first consisting of frozen samples from 132 stage II patients; and the second consisting of FFPE samples from the PETACC-3 trial (n = 625). The 64-gene MSI signature identified MSI patients in the first validation set with a sensitivity of 90.3% and an overall accuracy of 84.8%, with an AUC of 0.942 (95% CI, 0.888-0.975). In the second validation, the signature also showed excellent performance, with a sensitivity 94.3% and an overall accuracy of 90.6%, with an AUC of 0.965 (95% CI, 0.943-0.988). Besides correct identification of MSI patients, the gene signature identified a group of MSI-like patients that were MSS by standard assessment but MSI by signature assessment. The MSI-signature could be linked to a deficient MMR phenotype, as both MSI and MSI-like patients showed a high mutation frequency (8.2% and 6.4% of 615 genes assayed, respectively) as compared to patients classified as MSS (1.6% mutation frequency). The MSI signature showed prognostic power in stage II patients (n = 215) with a hazard ratio of 0.252 (p = 0.0145). Patients with an MSI-like phenotype had also an improved survival when compared to MSS patients. The MSI signature was translated to a diagnostic microarray and technically and clinically validated in FFPE and frozen samples. Copyright (C) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Citovat

TIAN, Sun; Paul ROEPMAN; Vlad POPOVICI; Magali MICHAUT; Ian MAJEWSKI; Ramon SALAZAR; Cristina SANTOS; Robert ROSENBERG; Ulrich NITSCHE; Wilma E MESKER; Sjoerd BRUIN; Sabine TEJPAR; Mauro DELORENZI; Rene BERNARDS a Iris SIMON. A robust genomic signature for the detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequency. JOURNAL OF PATHOLOGY. HOBOKEN: WILEY-BLACKWELL, 2012, roč. 228, č. 4, s. 586-595. ISSN 0022-3417. Dostupné z: https://doi.org/10.1002/path.4092.

@article{1090299,
   author = {Tian, Sun and Roepman, Paul and Popovici, Vlad and Michaut, Magali and Majewski, Ian and Salazar, Ramon and Santos, Cristina and Rosenberg, Robert and Nitsche, Ulrich and Mesker, Wilma E and Bruin, Sjoerd and Tejpar, Sabine and Delorenzi, Mauro and Bernards, Rene and Simon, Iris},
   article_location = {HOBOKEN},
   article_number = {4},
   doi = {https://doi.org/10.1002/path.4092},
   keywords = {Colorectal cancer; microsatellite instability; deficient mismatch repair system; gene expression; mutation frequency; genomic signature; prognosis},
   language = {eng},
   issn = {0022-3417},
   journal = {JOURNAL OF PATHOLOGY},
   title = {A robust genomic signature for the detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequency},
   volume = {228},
   year = {2012}
}

TY  - JOUR
ID  - 1090299
AU  - Tian, Sun - Roepman, Paul - Popovici, Vlad - Michaut, Magali - Majewski, Ian - Salazar, Ramon - Santos, Cristina - Rosenberg, Robert - Nitsche, Ulrich - Mesker, Wilma E - Bruin, Sjoerd - Tejpar, Sabine - Delorenzi, Mauro - Bernards, Rene - Simon, Iris
PY  - 2012
TI  - A robust genomic signature for the detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequency
JF  - JOURNAL OF PATHOLOGY
VL  - 228
IS  - 4
SP  - 586-595
EP  - 586-595
PB  - WILEY-BLACKWELL
SN  - 00223417
KW  - Colorectal cancer
KW  - microsatellite instability
KW  - deficient mismatch repair system
KW  - gene expression
KW  - mutation frequency
KW  - genomic signature
KW  - prognosis
N2  - Microsatellite instability (MSI) occurs in 10-20% of colorectal tumours and is associated with good prognosis. Here we describe the development and validation of a genomic signature that identifies colorectal cancer patients with MSI caused by DNA mismatch repair deficiency with high accuracy. Microsatellite status for 276 stage II and III colorectal tumours has been determined. Full-genome expression data was used to identify genes that correlate with MSI status. A subset of these samples (n = 73) had sequencing data for 615 genes available. An MSI gene signature of 64 genes was developed and validated in two independent validation sets: the first consisting of frozen samples from 132 stage II patients; and the second consisting of FFPE samples from the PETACC-3 trial (n = 625). The 64-gene MSI signature identified MSI patients in the first validation set with a sensitivity of 90.3% and an overall accuracy of 84.8%, with an AUC of 0.942 (95% CI, 0.888-0.975). In the second validation, the signature also showed excellent performance, with a sensitivity 94.3% and an overall accuracy of 90.6%, with an AUC of 0.965 (95% CI, 0.943-0.988). Besides correct identification of MSI patients, the gene signature identified a group of MSI-like patients that were MSS by standard assessment but MSI by signature assessment. The MSI-signature could be linked to a deficient MMR phenotype, as both MSI and MSI-like patients showed a high mutation frequency (8.2% and 6.4% of 615 genes assayed, respectively) as compared to patients classified as MSS (1.6% mutation frequency). The MSI signature showed prognostic power in stage II patients (n = 215) with a hazard ratio of 0.252 (p = 0.0145). Patients with an MSI-like phenotype had also an improved survival when compared to MSS patients. The MSI signature was translated to a diagnostic microarray and technically and clinically validated in FFPE and frozen samples. Copyright (C) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
ER  -

TIAN, Sun; Paul ROEPMAN; Vlad POPOVICI; Magali MICHAUT; Ian MAJEWSKI; Ramon SALAZAR; Cristina SANTOS; Robert ROSENBERG; Ulrich NITSCHE; Wilma E MESKER; Sjoerd BRUIN; Sabine TEJPAR; Mauro DELORENZI; Rene BERNARDS a Iris SIMON. A robust genomic signature for the detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequency. \textit{JOURNAL OF PATHOLOGY}. HOBOKEN: WILEY-BLACKWELL, 2012, roč.~228, č.~4, s.~586-595. ISSN~0022-3417. Dostupné z: https://doi.org/10.1002/path.4092.

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