Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours

Research output: Contribution to journalArticlepeer-review

Standard

Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours. / Izquierdo, Elisa; Yuan, Lina; George, Sally; Hubank, Michael; Jones, Chris; Proszek, Paula; Shipley, Janet; Gatz, Susanne A; Stinson, Caedyn; Moore, Andrew S; Clifford, Steven C; Hicks, Debbie; Lindsey, Janet C; Hill, Rebecca M; Jacques, Thomas S; Chalker, Jane; Thway, Khin; O'Connor, Simon; Marshall, Lynley; Moreno, Lucas; Pearson, Andrew; Chesler, Louis; Walker, Brian A; De Castro, David Gonzalez.

In: OncoTarget, Vol. 8, No. 67, 06.12.2017, p. 112036-112050.

Research output: Contribution to journalArticlepeer-review

Harvard

Izquierdo, E, Yuan, L, George, S, Hubank, M, Jones, C, Proszek, P, Shipley, J, Gatz, SA, Stinson, C, Moore, AS, Clifford, SC, Hicks, D, Lindsey, JC, Hill, RM, Jacques, TS, Chalker, J, Thway, K, O'Connor, S, Marshall, L, Moreno, L, Pearson, A, Chesler, L, Walker, BA & De Castro, DG 2017, 'Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours', OncoTarget, vol. 8, no. 67, pp. 112036-112050. https://doi.org/10.18632/oncotarget.23000

APA

Izquierdo, E., Yuan, L., George, S., Hubank, M., Jones, C., Proszek, P., Shipley, J., Gatz, S. A., Stinson, C., Moore, A. S., Clifford, S. C., Hicks, D., Lindsey, J. C., Hill, R. M., Jacques, T. S., Chalker, J., Thway, K., O'Connor, S., Marshall, L., ... De Castro, D. G. (2017). Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours. OncoTarget, 8(67), 112036-112050. https://doi.org/10.18632/oncotarget.23000

Vancouver

Author

Izquierdo, Elisa ; Yuan, Lina ; George, Sally ; Hubank, Michael ; Jones, Chris ; Proszek, Paula ; Shipley, Janet ; Gatz, Susanne A ; Stinson, Caedyn ; Moore, Andrew S ; Clifford, Steven C ; Hicks, Debbie ; Lindsey, Janet C ; Hill, Rebecca M ; Jacques, Thomas S ; Chalker, Jane ; Thway, Khin ; O'Connor, Simon ; Marshall, Lynley ; Moreno, Lucas ; Pearson, Andrew ; Chesler, Louis ; Walker, Brian A ; De Castro, David Gonzalez. / Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours. In: OncoTarget. 2017 ; Vol. 8, No. 67. pp. 112036-112050.

Bibtex

@article{d654008b2ba64daea0b5b354f72a35b7,
title = "Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours",
abstract = "The implementation of personalised medicine in childhood cancers has been limited by a lack of clinically validated multi-target sequencing approaches specific for paediatric solid tumours. In order to support innovative clinical trials in high-risk patients with unmet need, we have developed a clinically relevant targeted sequencing panel spanning 311 kb and comprising 78 genes involved in childhood cancers. A total of 132 samples were used for the validation of the panel, including Horizon Discovery cell blends (n=4), cell lines (n=15), formalin-fixed paraffin embedded (FFPE, n=83) and fresh frozen tissue (FF, n=30) patient samples. Cell blends containing known single nucleotide variants (SNVs, n=528) and small insertion-deletions (indels n=108) were used to define panel sensitivities of ≥98% for SNVs and ≥83% for indels [95% CI] and panel specificity of ≥98% [95% CI] for SNVs. FFPE samples performed comparably to FF samples (n=15 paired). Of 95 well-characterised genetic abnormalities in 33 clinical specimens and 13 cell lines (including SNVs, indels, amplifications, rearrangements and chromosome losses), 94 (98.9%) were detected by our approach. We have validated a robust and practical methodology to guide clinical management of children with solid tumours based on their molecular profiles. Our work demonstrates the value of targeted gene sequencing in the development of precision medicine strategies in paediatric oncology.",
author = "Elisa Izquierdo and Lina Yuan and Sally George and Michael Hubank and Chris Jones and Paula Proszek and Janet Shipley and Gatz, {Susanne A} and Caedyn Stinson and Moore, {Andrew S} and Clifford, {Steven C} and Debbie Hicks and Lindsey, {Janet C} and Hill, {Rebecca M} and Jacques, {Thomas S} and Jane Chalker and Khin Thway and Simon O'Connor and Lynley Marshall and Lucas Moreno and Andrew Pearson and Louis Chesler and Walker, {Brian A} and {De Castro}, {David Gonzalez}",
year = "2017",
month = dec,
day = "6",
doi = "10.18632/oncotarget.23000",
language = "English",
volume = "8",
pages = "112036--112050",
journal = "OncoTarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "67",

}

RIS

TY - JOUR

T1 - Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours

AU - Izquierdo, Elisa

AU - Yuan, Lina

AU - George, Sally

AU - Hubank, Michael

AU - Jones, Chris

AU - Proszek, Paula

AU - Shipley, Janet

AU - Gatz, Susanne A

AU - Stinson, Caedyn

AU - Moore, Andrew S

AU - Clifford, Steven C

AU - Hicks, Debbie

AU - Lindsey, Janet C

AU - Hill, Rebecca M

AU - Jacques, Thomas S

AU - Chalker, Jane

AU - Thway, Khin

AU - O'Connor, Simon

AU - Marshall, Lynley

AU - Moreno, Lucas

AU - Pearson, Andrew

AU - Chesler, Louis

AU - Walker, Brian A

AU - De Castro, David Gonzalez

PY - 2017/12/6

Y1 - 2017/12/6

N2 - The implementation of personalised medicine in childhood cancers has been limited by a lack of clinically validated multi-target sequencing approaches specific for paediatric solid tumours. In order to support innovative clinical trials in high-risk patients with unmet need, we have developed a clinically relevant targeted sequencing panel spanning 311 kb and comprising 78 genes involved in childhood cancers. A total of 132 samples were used for the validation of the panel, including Horizon Discovery cell blends (n=4), cell lines (n=15), formalin-fixed paraffin embedded (FFPE, n=83) and fresh frozen tissue (FF, n=30) patient samples. Cell blends containing known single nucleotide variants (SNVs, n=528) and small insertion-deletions (indels n=108) were used to define panel sensitivities of ≥98% for SNVs and ≥83% for indels [95% CI] and panel specificity of ≥98% [95% CI] for SNVs. FFPE samples performed comparably to FF samples (n=15 paired). Of 95 well-characterised genetic abnormalities in 33 clinical specimens and 13 cell lines (including SNVs, indels, amplifications, rearrangements and chromosome losses), 94 (98.9%) were detected by our approach. We have validated a robust and practical methodology to guide clinical management of children with solid tumours based on their molecular profiles. Our work demonstrates the value of targeted gene sequencing in the development of precision medicine strategies in paediatric oncology.

AB - The implementation of personalised medicine in childhood cancers has been limited by a lack of clinically validated multi-target sequencing approaches specific for paediatric solid tumours. In order to support innovative clinical trials in high-risk patients with unmet need, we have developed a clinically relevant targeted sequencing panel spanning 311 kb and comprising 78 genes involved in childhood cancers. A total of 132 samples were used for the validation of the panel, including Horizon Discovery cell blends (n=4), cell lines (n=15), formalin-fixed paraffin embedded (FFPE, n=83) and fresh frozen tissue (FF, n=30) patient samples. Cell blends containing known single nucleotide variants (SNVs, n=528) and small insertion-deletions (indels n=108) were used to define panel sensitivities of ≥98% for SNVs and ≥83% for indels [95% CI] and panel specificity of ≥98% [95% CI] for SNVs. FFPE samples performed comparably to FF samples (n=15 paired). Of 95 well-characterised genetic abnormalities in 33 clinical specimens and 13 cell lines (including SNVs, indels, amplifications, rearrangements and chromosome losses), 94 (98.9%) were detected by our approach. We have validated a robust and practical methodology to guide clinical management of children with solid tumours based on their molecular profiles. Our work demonstrates the value of targeted gene sequencing in the development of precision medicine strategies in paediatric oncology.

U2 - 10.18632/oncotarget.23000

DO - 10.18632/oncotarget.23000

M3 - Article

C2 - 29340109

VL - 8

SP - 112036

EP - 112050

JO - OncoTarget

JF - OncoTarget

SN - 1949-2553

IS - 67

ER -