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
References
May 31, 2001·International Journal of Radiation Oncology, Biology, Physics·S TribiusD Casper
Sep 24, 2004·International Journal of Cancer. Journal International Du Cancer·Alfa H C BaiWai K Leung
Dec 18, 2004·Cancer Research·Ian HicksonGraeme C M Smith
Mar 15, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Heike GrabschWolfram Mueller
Jul 18, 2009·Genes & Development·Hai JiangMichael T Hemann
Jul 20, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Jul 24, 2012·Breast Cancer Research : BCR·Tomasz ByrskiSteven A Narod
Nov 17, 2012·Oncotarget·Andrew D BeggsIan P M Tomlinson
Mar 15, 2013·Nature Reviews. Molecular Cell Biology·Yosef Shiloh, Yael Ziv
Mar 20, 2013·Proceedings of the National Academy of Sciences of the United States of America·Elizabeth M KassMaria Jasin
Apr 27, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Laura Biddlestone-ThorpeKristoffer Valerie
Jul 16, 2013·Oncogene·C A Cremona, A Behrens
Nov 19, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kathryn P PenningtonElizabeth M Swisher
Jun 14, 2014·Oncology·Filippo PietrantonioFilippo de Braud
Aug 19, 2014·Breast Cancer Research and Treatment·T ByrskiS A Narod
Apr 9, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·N NormannoUNKNOWN CAPRI-GOIM investigators
Oct 29, 2015·The New England Journal of Medicine·Joaquin MateoJohann S de Bono
Nov 23, 2015·Molecular Cell·Mark J O'Connor
Feb 21, 2016·Pharmacology & Therapeutics·Navnath S GavandeJohn J Turchi
Jan 1, 2014·Molecular & Cellular Oncology·Johannes WinklerShuhua Chen
Jul 15, 2016·Molecular Cancer Therapeutics·Michael ChoiRazelle Kurzrock
Nov 1, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Filippo PietrantonioFilippo de Braud
Dec 9, 2016·Nature Communications·Beth O Van EmburghAlberto Bardelli
Dec 17, 2016·Clinical Colorectal Cancer·Filippo PietrantonioVincenzo Mazzaferro
Jan 5, 2017·Nature Reviews. Cancer·Rodrigo DienstmannJosep Tabernero
Jan 10, 2017·International Journal of Molecular Sciences·Angelika CopijaEwa Nowakowska-Zajdel
Feb 10, 2017·Translational Oncology·Chen WangSusan P Lees-Miller
Jun 18, 2017·Molecular Cell·Andrew N Blackford, Stephen P Jackson
Oct 19, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C CremoliniF Pietrantonio
Nov 22, 2017·Oncotarget·Mohamed E SalemJohn L Marshall
Dec 7, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Filippo PietrantonioMaria Di Bartolomeo
Citations
Nov 11, 2019·Nature Reviews. Clinical Oncology·Christopher Nevala-PlagemannIgnacio Garrido-Laguna
Sep 15, 2020·JCO Precision Oncology·Danielle M FileSimon Khagi
Jan 23, 2020·World Journal of Gastrointestinal Oncology·Tasuku Matsuoka, Masakazu Yashiro
Jul 25, 2019·Cancers·Thoranin IntarajakSupapon Cheevadhanarak
Jan 8, 2021·Journal of Experimental & Clinical Cancer Research : CR·Pietro Paolo VitielloErika Martinelli
Mar 4, 2021·BMC Cancer·Peng-Chan LinMeng-Ru Shen
Apr 16, 2021·Scientific Reports·Chul Seung LeeSung Hak Lee
Apr 16, 2021·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Pedro L S UsonNiloy Jewel Samadder
May 18, 2021·Frontiers in Oncology·Qin LiuFanxin Zeng
Oct 31, 2020·Clinical Colorectal Cancer·Erin McGillivrayRishi Jain
Jul 3, 2021·Cancers·Paula Pellenz TomasiniJenifer Saffi
Jul 23, 2021·OncoTargets and Therapy·Yu ChengXiujuan Qu
Aug 17, 2021·Pancreas·Andrew TrunkIgnacio Garrido-Laguna
Jun 9, 2020·Annals of Oncology : Official Journal of the European Society for Medical Oncology·G MauriA Sartore-Bianchi
Jan 15, 2022·Cancer Communications·Caroline Moraes BeltramiSilvia Regina Rogatto