Multi-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss

Andrew M. Gross; Ryan K. Orosco; John P. Shen; Ann Marie Egloff; Hannah Carter; Matan Hofree; Michel Choueiri; Charles S. Coffey; Scott M. Lippman; D. Neil Hayes; Ezra E. Cohen; Jennifer R. Grandis; Quyen T. Nguyen; Trey Ideker

doi:10.1038/ng.3051

Multi-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss

Andrew M. Gross, Ryan K. Orosco, John P. Shen, Ann Marie Egloff, Hannah Carter, Matan Hofree, Michel Choueiri, Charles S. Coffey, Scott M. Lippman, D. Neil Hayes, Ezra E. Cohen, Jennifer R. Grandis, Quyen T. Nguyen, Trey Ideker^*

^*Corresponding author for this work

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

103 Scopus citations

Abstract

Head and neck squamous cell carcinoma (HNSCC) is characterized by aggressive behavior with a propensity for metastasis and recurrence. Here we report a comprehensive analysis of the molecular and clinical features of HNSCC that govern patient survival. We find that TP53 mutation is frequently accompanied by loss of chromosome 3p and that the combination of these events is associated with a surprising decrease in survival time (1.9 years versus >5 years for TP53 mutation alone). The TP53-3p interaction is specific to chromosome 3p and validates in HNSCC and pan-cancer cohorts. In human papillomavirus (HPV)-positive tumors, in which HPV inactivates TP53, 3p deletion is also common and is associated with poor outcomes. The TP53-3p event is modified by mir-548k expression, which decreases survival further, and is mutually exclusive with mutations affecting RAS signaling. Together, the identified markers underscore the molecular heterogeneity of HNSCC and enable a new multi-tiered classification of this disease.

Original language	English
Pages (from-to)	939-943
Number of pages	5
Journal	Nature Genetics
Volume	46
Issue number	9
DOIs	https://doi.org/10.1038/ng.3051
State	Published - 2014
Externally published	Yes

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© 2014 Nature America, Inc. All rights reserved.

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title = "Multi-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss",

abstract = "Head and neck squamous cell carcinoma (HNSCC) is characterized by aggressive behavior with a propensity for metastasis and recurrence. Here we report a comprehensive analysis of the molecular and clinical features of HNSCC that govern patient survival. We find that TP53 mutation is frequently accompanied by loss of chromosome 3p and that the combination of these events is associated with a surprising decrease in survival time (1.9 years versus >5 years for TP53 mutation alone). The TP53-3p interaction is specific to chromosome 3p and validates in HNSCC and pan-cancer cohorts. In human papillomavirus (HPV)-positive tumors, in which HPV inactivates TP53, 3p deletion is also common and is associated with poor outcomes. The TP53-3p event is modified by mir-548k expression, which decreases survival further, and is mutually exclusive with mutations affecting RAS signaling. Together, the identified markers underscore the molecular heterogeneity of HNSCC and enable a new multi-tiered classification of this disease.",

author = "Gross, {Andrew M.} and Orosco, {Ryan K.} and Shen, {John P.} and Egloff, {Ann Marie} and Hannah Carter and Matan Hofree and Michel Choueiri and Coffey, {Charles S.} and Lippman, {Scott M.} and Hayes, {D. Neil} and Cohen, {Ezra E.} and Grandis, {Jennifer R.} and Nguyen, {Quyen T.} and Trey Ideker",

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AU - Egloff, Ann Marie

AU - Carter, Hannah

AU - Hofree, Matan

AU - Choueiri, Michel

AU - Coffey, Charles S.

AU - Lippman, Scott M.

AU - Hayes, D. Neil

AU - Cohen, Ezra E.

AU - Grandis, Jennifer R.

AU - Nguyen, Quyen T.

AU - Ideker, Trey

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AB - Head and neck squamous cell carcinoma (HNSCC) is characterized by aggressive behavior with a propensity for metastasis and recurrence. Here we report a comprehensive analysis of the molecular and clinical features of HNSCC that govern patient survival. We find that TP53 mutation is frequently accompanied by loss of chromosome 3p and that the combination of these events is associated with a surprising decrease in survival time (1.9 years versus >5 years for TP53 mutation alone). The TP53-3p interaction is specific to chromosome 3p and validates in HNSCC and pan-cancer cohorts. In human papillomavirus (HPV)-positive tumors, in which HPV inactivates TP53, 3p deletion is also common and is associated with poor outcomes. The TP53-3p event is modified by mir-548k expression, which decreases survival further, and is mutually exclusive with mutations affecting RAS signaling. Together, the identified markers underscore the molecular heterogeneity of HNSCC and enable a new multi-tiered classification of this disease.

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Multi-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss

Abstract

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