The importance of p53 pathway genetics in inherited and somatic cancer genomes

Giovanni Stracquadanio; Xuting Wang; Marsha D Wallace; Anna M Grawenda; Ping Zhang; Juliet Hewitt; Jorge Zeron-Medina; Francesc Castro-Giner; Ian P Tomlinson; Colin R Goding; Kamil J Cygan; William G Fairbrother; Laurent F Thomas; Pål Sætrom; Federica Gemignani; Stefano Landi; Benjamin Schuster-Böckler; Douglas A Bell; Gareth L Bond

doi:10.1038/nrc.2016.15

The importance of p53 pathway genetics in inherited and somatic cancer genomes

Giovanni Stracquadanio, Xuting Wang, Marsha D Wallace, Anna M Grawenda, Ping Zhang, Juliet Hewitt, Jorge Zeron-Medina, Francesc Castro-Giner, Ian P Tomlinson, Colin R Goding, Kamil J Cygan, William G Fairbrother, Laurent F Thomas, Pål Sætrom, Federica Gemignani, Stefano Landi, Benjamin Schuster-Böckler, Douglas A Bell, Gareth L Bond

Research output: Contribution to journal › Review article › peer-review

Abstract / Description of output

Decades of research have shown that mutations in the p53 stress response pathway affect the incidence of diverse cancers more than mutations in other pathways. However, most evidence is limited to somatic mutations and rare inherited mutations. Using newly abundant genomic data, we demonstrate that commonly inherited genetic variants in the p53 pathway also affect the incidence of a broad range of cancers more than variants in other pathways. The cancer-associated single nucleotide polymorphisms (SNPs) of the p53 pathway have strikingly similar genetic characteristics to well-studied p53 pathway cancer-causing somatic mutations. Our results enable insights into p53-mediated tumour suppression in humans and into p53 pathway-based cancer surveillance and treatment strategies.

Original language	English
Pages (from-to)	251-65
Number of pages	15
Journal	Nature Reviews Cancer
Volume	16
Issue number	4
DOIs	https://doi.org/10.1038/nrc.2016.15
Publication status	Published - 1 Apr 2016

Keywords / Materials (for Non-textual outputs)

Genetic Predisposition to Disease/genetics
Genome, Human
Humans
Mutation
Neoplasms/genetics
Polymorphism, Single Nucleotide/genetics
Tumor Suppressor Protein p53/genetics

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10.1038/nrc.2016.15

Giovanni Stracquadanio
- School of Biological Sciences - Personal Chair in Engineering Biology
- Centre for Engineering Biology
Person: Academic: Research Active

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Stracquadanio, G., Wang, X., Wallace, M. D., Grawenda, A. M., Zhang, P., Hewitt, J., Zeron-Medina, J., Castro-Giner, F., Tomlinson, I. P., Goding, C. R., Cygan, K. J., Fairbrother, W. G., Thomas, L. F., Sætrom, P., Gemignani, F., Landi, S., Schuster-Böckler, B., Bell, D. A., & Bond, G. L. (2016). The importance of p53 pathway genetics in inherited and somatic cancer genomes. Nature Reviews Cancer, 16(4), 251-65. https://doi.org/10.1038/nrc.2016.15

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title = "The importance of p53 pathway genetics in inherited and somatic cancer genomes",

abstract = "Decades of research have shown that mutations in the p53 stress response pathway affect the incidence of diverse cancers more than mutations in other pathways. However, most evidence is limited to somatic mutations and rare inherited mutations. Using newly abundant genomic data, we demonstrate that commonly inherited genetic variants in the p53 pathway also affect the incidence of a broad range of cancers more than variants in other pathways. The cancer-associated single nucleotide polymorphisms (SNPs) of the p53 pathway have strikingly similar genetic characteristics to well-studied p53 pathway cancer-causing somatic mutations. Our results enable insights into p53-mediated tumour suppression in humans and into p53 pathway-based cancer surveillance and treatment strategies. ",

keywords = "Genetic Predisposition to Disease/genetics, Genome, Human, Humans, Mutation, Neoplasms/genetics, Polymorphism, Single Nucleotide/genetics, Tumor Suppressor Protein p53/genetics",

author = "Giovanni Stracquadanio and Xuting Wang and Wallace, {Marsha D} and Grawenda, {Anna M} and Ping Zhang and Juliet Hewitt and Jorge Zeron-Medina and Francesc Castro-Giner and Tomlinson, {Ian P} and Goding, {Colin R} and Cygan, {Kamil J} and Fairbrother, {William G} and Thomas, {Laurent F} and P{\aa}l S{\ae}trom and Federica Gemignani and Stefano Landi and Benjamin Schuster-B{\"o}ckler and Bell, {Douglas A} and Bond, {Gareth L}",

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year = "2016",

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doi = "10.1038/nrc.2016.15",

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Stracquadanio, G, Wang, X, Wallace, MD, Grawenda, AM, Zhang, P, Hewitt, J, Zeron-Medina, J, Castro-Giner, F, Tomlinson, IP, Goding, CR, Cygan, KJ, Fairbrother, WG, Thomas, LF, Sætrom, P, Gemignani, F, Landi, S, Schuster-Böckler, B, Bell, DA & Bond, GL 2016, 'The importance of p53 pathway genetics in inherited and somatic cancer genomes', Nature Reviews Cancer, vol. 16, no. 4, pp. 251-65. https://doi.org/10.1038/nrc.2016.15

TY - JOUR

T1 - The importance of p53 pathway genetics in inherited and somatic cancer genomes

AU - Stracquadanio, Giovanni

AU - Wang, Xuting

AU - Wallace, Marsha D

AU - Grawenda, Anna M

AU - Zhang, Ping

AU - Hewitt, Juliet

AU - Zeron-Medina, Jorge

AU - Castro-Giner, Francesc

AU - Tomlinson, Ian P

AU - Goding, Colin R

AU - Cygan, Kamil J

AU - Fairbrother, William G

AU - Thomas, Laurent F

AU - Sætrom, Pål

AU - Gemignani, Federica

AU - Landi, Stefano

AU - Schuster-Böckler, Benjamin

AU - Bell, Douglas A

AU - Bond, Gareth L

N1 - I have requested the DoA to PI 23/04/2019 EN

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Decades of research have shown that mutations in the p53 stress response pathway affect the incidence of diverse cancers more than mutations in other pathways. However, most evidence is limited to somatic mutations and rare inherited mutations. Using newly abundant genomic data, we demonstrate that commonly inherited genetic variants in the p53 pathway also affect the incidence of a broad range of cancers more than variants in other pathways. The cancer-associated single nucleotide polymorphisms (SNPs) of the p53 pathway have strikingly similar genetic characteristics to well-studied p53 pathway cancer-causing somatic mutations. Our results enable insights into p53-mediated tumour suppression in humans and into p53 pathway-based cancer surveillance and treatment strategies.

AB - Decades of research have shown that mutations in the p53 stress response pathway affect the incidence of diverse cancers more than mutations in other pathways. However, most evidence is limited to somatic mutations and rare inherited mutations. Using newly abundant genomic data, we demonstrate that commonly inherited genetic variants in the p53 pathway also affect the incidence of a broad range of cancers more than variants in other pathways. The cancer-associated single nucleotide polymorphisms (SNPs) of the p53 pathway have strikingly similar genetic characteristics to well-studied p53 pathway cancer-causing somatic mutations. Our results enable insights into p53-mediated tumour suppression in humans and into p53 pathway-based cancer surveillance and treatment strategies.

KW - Genetic Predisposition to Disease/genetics

KW - Genome, Human

KW - Humans

KW - Mutation

KW - Neoplasms/genetics

KW - Polymorphism, Single Nucleotide/genetics

KW - Tumor Suppressor Protein p53/genetics

U2 - 10.1038/nrc.2016.15

DO - 10.1038/nrc.2016.15

M3 - Review article

C2 - 27009395

SN - 1474-175X

VL - 16

SP - 251

EP - 265

JO - Nature Reviews Cancer

JF - Nature Reviews Cancer

IS - 4

ER -

The importance of p53 pathway genetics in inherited and somatic cancer genomes

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Keywords / Materials (for Non-textual outputs)

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Giovanni Stracquadanio

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