Prognostic impact of ATM mutations in patients with metastatic colorectal cancer

Scientific Reports
Giovanni RandonF Pietrantonio

Abstract

Tumors bearing homologous recombination deficiency are extremely sensitive to DNA double strand breaks induced by several chemotherapeutic agents. ATM gene, encoding a protein involved in DNA damage response, is frequently mutated in colorectal cancer (CRC), but its potential role as predictive and prognostic biomarker has not been fully investigated. We carried out a multicenter effort aimed at defining the prognostic impact of ATM mutational status in metastatic CRC (mCRC) patients. Mutational profiles were obtained by means of next-generation sequencing. Overall, 35 out of 227 samples (15%) carried an ATM mutation. At a median follow-up of 56.6 months, patients with ATM mutated tumors showed a significantly longer median overall survival (OS) versus ATM wild-type ones (64.9 vs 34.8 months; HR, 0.50; 95% CI, 0.29-0.85; P = 0.01). In the multivariable model, ATM mutations confirmed the association with longer OS (HR, 0.57; 95% CI, 0.33-0.98; P = 0.04). The prognostic impact of ATM mutations was independent from TP53 mutational status and primary tumor location. High heterogeneity score for ATM mutations, possibly reflecting the loss of wild-type allele, was associated with excellent prognosis. In conclusion, we showed that ATM...Continue Reading

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Citations

Nov 11, 2019·Nature Reviews. Clinical Oncology·Christopher Nevala-PlagemannIgnacio Garrido-Laguna
Jan 23, 2020·World Journal of Gastrointestinal Oncology·Tasuku Matsuoka, Masakazu Yashiro
Jan 8, 2021·Journal of Experimental & Clinical Cancer Research : CR·Pietro Paolo VitielloErika Martinelli
Apr 16, 2021·Scientific Reports·Chul Seung LeeSung Hak Lee
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Jan 15, 2022·Cancer Communications·Caroline Moraes BeltramiSilvia Regina Rogatto

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