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Comprehensive characterization of PTEN mutational profile in a series of 34,129 colorectal cancers

Serebriiskii, Ilya G.
; 
Pavlov, Valery
; ; 
Andrianov, Gregory
; 
Nicolas, Emmanuelle
; ; 
Newberg, Justin
; 
Frampton, Garrett
; 
Meyer, Joshua E.
; 
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Genre
Journal article
Date
2022-03-25
Advisor
Committee member
Group
Fox Chase Cancer Center (Temple University)
Department
Cancer and Cellular Biology
Subject
Cancer genetics
 Cancer genomics
 Colorectal cancer
 Tumour-suppressor proteins
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http://hdl.handle.net/20.500.12613/9191
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GolemisEtAl-JournalArticle-2022-03.pdf
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http://dx.doi.org/10.1038/s41467-022-29227-2
Abstract
Loss of expression or activity of the tumor suppressor PTEN acts similarly to an activating mutation in the oncogene PIK3CA in elevating intracellular levels of phosphatidylinositol (3,4,5)-trisphosphate (PIP3), inducing signaling by AKT and other pro-tumorigenic signaling proteins. Here, we analyze sequence data for 34,129 colorectal cancer (CRC) patients, capturing 3,434 PTEN mutations. We identify specific patterns of PTEN mutation associated with microsatellite stability/instability (MSS/MSI), tumor mutational burden (TMB), patient age, and tumor location. Within groups separated by MSS/MSI status, this identifies distinct profiles of nucleotide hotspots, and suggests differing profiles of protein-damaging effects of mutations. Moreover, discrete categories of PTEN mutations display non-identical patterns of co-occurrence with mutations in other genes important in CRC pathogenesis, including KRAS, APC, TP53, and PIK3CA. These data provide context for clinical targeting of proteins upstream and downstream of PTEN in distinct CRC cohorts.
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Citation
Serebriiskii IG, Pavlov V, Tricarico R, Andrianov G, Nicolas E, Parker MI, et al. Comprehensive characterization of PTEN mutational profile in a series of 34,129 colorectal cancers. Nat Commun. 2022 Mar 25;13:1618. doi:10.1038/s41467-022-29227-2.
Citation to related work
Springer Nature
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Nature Communications, Vol. 13
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