Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian Cancer

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Rachel N GrishamGopa Iyer

Abstract

No effective systemic therapy exists for patients with metastatic low-grade serous (LGS) ovarian cancers. BRAF and KRAS mutations are common in serous borderline (SB) and LGS ovarian cancers, and MEK inhibition has been shown to induce tumor regression in a minority of patients; however, no correlation has been observed between mutation status and clinical response. With the goal of identifying biomarkers of sensitivity to MEK inhibitor treatment, we performed an outlier analysis of a patient who experienced a complete, durable, and ongoing (> 5 years) response to selumetinib, a non-ATP competitive MEK inhibitor. Next-generation sequencing was used to analyze this patient's tumor as well as an additional 28 SB/LGS tumors. Functional characterization of an identified novel alteration of interest was performed. Analysis of the extraordinary responder's tumor identified a 15-nucleotide deletion in the negative regulatory helix of the MAP2K1 gene encoding for MEK1. Functional characterization demonstrated that this mutant induced extracellular signal-regulated kinase pathway activation, promoted anchorage-independent growth and tumor formation in mice, and retained sensitivity to selumetinib. Analysis of additional LGS/SB tumors id...Continue Reading

References

Mar 20, 2003·Journal of the National Cancer Institute·Gad SingerIe-Ming Shih
May 27, 2003·The American Journal of Surgical Pathology·Ann E Smith SehdevRobert J Kurman
May 14, 2004·The Journal of Pathology·S E Hilary Russell, W Glenn McCluggage
Nov 8, 2005·Nature·David B SolitNeal Rosen
Dec 25, 2007·Gynecologic Oncology·Kathleen M SchmelerDavid M Gershenson
Jan 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·Samanthi A PereraKwok-Kin Wong
Mar 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Christine A PratilasNeal Rosen
Apr 14, 2009·Gynecologic Oncology·David M GershensonJohn J Kavanagh
Aug 31, 2010·The American Journal of Pathology·Kwong-Kwok WongDavid M Gershenson
Jul 2, 2011·Nature·UNKNOWN Cancer Genome Atlas Research Network
Nov 22, 2011·The Journal of Pathology·Siân JonesIe-Ming Shih
Dec 7, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Neerav ShuklaMarc Ladanyi
Jun 6, 2012·The New England Journal of Medicine·Keith T FlahertyUNKNOWN METRIC Study Group
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
Jun 19, 2013·Gynecologic Oncology·Jeff BoydHong Wu
Jul 3, 2013·Nature Genetics·David T W JonesUNKNOWN International Cancer Genome Consortium PedBrain Tumor Project
Dec 19, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Katherine E HutchinsonWilliam Pao

❮ Previous
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Citations

May 4, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A Malpica, K-K Wong
May 4, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·D M Gershenson
May 4, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J KrzystyniakM J Birrer
Jul 30, 2016·Pharmacogenomics·Jennifer McLachlanSusana Banerjee
Nov 3, 2016·Nature Reviews. Clinical Oncology·Juanita S Lopez, Udai Banerji
Jan 13, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·David M HymanAlexia Iasonos
Jan 4, 2017·The American Journal of Dermatopathology·J Andrew CarlsonJeffrey S Ross
Mar 1, 2018·AJR. American Journal of Roentgenology·Stephanie NougaretEvis Sala
Jan 22, 2019·Genes, Chromosomes & Cancer·Aleksandra PfeiferBarbara Jarząb
Oct 30, 2019·Journal of Biomolecular Structure & Dynamics·Ye LiuWeiwei Han
Jul 27, 2017·American Society of Clinical Oncology Educational Book·Wafik S El-DeiryJoel W Neal
Jun 2, 2016·American Society of Clinical Oncology Educational Book·Keiichi FujiwaraAmit M Oza
Nov 1, 2018·Science Signaling·Jimin YuanJiancheng Hu
Dec 19, 2019·The Australian & New Zealand Journal of Obstetrics & Gynaecology·Elizabeth A GouldingPeter Sykes
Jun 5, 2020·Thyroid : Official Journal of the American Thyroid Association·Barbora PekovaBela Bendlova
Aug 22, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bradley J MonkIgnace Vergote
Sep 9, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·David M GershensonJames Paul
Jun 27, 2017·NPJ Breast Cancer·Kristine De La TorreUNKNOWN Metastatic Breast Cancer Alliance
Jan 15, 2019·Cancer Cell International·Marta Llaurado FernandezMark S Carey
Nov 19, 2019·Journal of Computer Assisted Tomography·Sherif B ElsherifPriya R Bhosale
May 12, 2019·Nature Reviews. Cancer·Flurina A M SanerDavid D L Bowtell
Apr 5, 2020·International Journal of Molecular Sciences·Jingxuan ZhuWeiwei Han
Feb 18, 2017·Breast Cancer Research and Treatment·Sahar NozadJon H Chung
Sep 19, 2018·Current Treatment Options in Oncology·Rachel N Grisham, Gopa Iyer
Jan 1, 2018·JCO Precision Oncology·Elizabeth H StoverPanagiotis A Konstantinopoulos
Jan 29, 2020·Current Oncology Reports·Nina PaulyThaïs Baert
May 3, 2018·Cancer Discovery·Joel D MaustJudith S Sebolt-Leopold
Jun 23, 2019·Cancer Discovery·Yijun GaoRona Yaeger
Jun 25, 2017·Cancer Research·Dariush EtemadmoghadamUNKNOWN Australian Ovarian Cancer Study Group
Apr 11, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Masataka TakenakaUNKNOWN Australian Ovarian Cancer Study Group
Oct 4, 2020·Cancer Research·Christopher E Whitehead, Judith S Sebolt-Leopold
Oct 4, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kazuhito SatoHiroyuki Mano
May 31, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rachel N GrishamCarol A Aghajanian
Jan 13, 2021·Cancer Cell·Arijh ElzeinDavid B Solit
Nov 16, 2019·Journal of Medicinal Chemistry·Jieli WeiJian Jin

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