title: Identification of a novel metabolic-related mutation (IDH1) in metastatic pancreatic cancer.
abstract: Isocitrate dehydrogenase 1 (IDH1) is a metabolic enzyme implicated in cancer cell metabolic reprogramming. This is underscored by the detection of functional, somatic IDH1 mutations frequently found in secondary glioblastoma. To our knowledge, there has never been a reported, validated case of an IDH1 mutation in a pancreatic ductal adenocarcinoma (PDA). Herein, we present a case of a patient with metastatic PDA that harbored a potentially actionable, albeit rare, IDH1 mutation. As part of the Know Your Tumor project (Pancreatic Cancer Action Network), a 48-year-old female was diagnosed with metastatic PDA and subsequently started on standard of care chemotherapy, during which her hepatic lesions progressed. Detailed molecular profiling was performed on a biopsy from a liver lesion that demonstrated an IDH1 mutation, R132H. This mutation was confirmed by an independent sequencing reaction from the tumor sample, and by immunohistochemistry using an antibody specific for the IDH1 R132H mutation. The patient subsequently received a mutant IDH1 inhibitor (AG-120, Agios Pharmaceuticals, Cambridge, MA), but with no response. IDH1 mutations are common in certain cancer types, but have not been reported in PDA. We report the first case of an IDH1 mutation in this tumor type, perhaps providing a rare opportunity for a targeted therapy as a treatment option for PDA.
authors.affiliation: a Department of Surgery , Jefferson Pancreas, Biliary and Related Cancer Center, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia , PA , USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Brody
authors.affiliation: a Department of Surgery , Jefferson Pancreas, Biliary and Related Cancer Center, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia , PA , USA.
authors.forename: Cinthya S
authors.initials: CS
authors.lastname: Yabar
authors.affiliation: a Department of Surgery , Jefferson Pancreas, Biliary and Related Cancer Center, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia , PA , USA.
authors.forename: Mahsa
authors.initials: M
authors.lastname: Zarei
authors.affiliation: b Perthera, Inc. , McLean , VA , USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Bender
authors.affiliation: c The Pancreatic Cancer Action Network , Manhattan Beach , CA , USA.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Matrisian
authors.affiliation: c The Pancreatic Cancer Action Network , Manhattan Beach , CA , USA.
authors.forename: Lola
authors.initials: L
authors.lastname: Rahib
authors.affiliation: b Perthera, Inc. , McLean , VA , USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Heartwell
authors.affiliation: b Perthera, Inc. , McLean , VA , USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Mason
authors.affiliation: a Department of Surgery , Jefferson Pancreas, Biliary and Related Cancer Center, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia , PA , USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
authors.affiliation: d Department of Pathology , Thomas Jefferson University , Philadelphia , PA , USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Peiper
authors.affiliation: d Department of Pathology , Thomas Jefferson University , Philadelphia , PA , USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: b Perthera, Inc. , McLean , VA , USA.
authors.forename: Katelyn
authors.initials: K
authors.lastname: Varieur
authors.affiliation: b Perthera, Inc. , McLean , VA , USA.|e Lombardi Comprehensive Cancer Center, Georgetown University Medical Center , Washington , DC , USA.
authors.forename: Subha
authors.initials: S
authors.lastname: Madhavan
authors.affiliation: b Perthera, Inc. , McLean , VA , USA.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Petricoin
authors.affiliation: d Department of Pathology , Thomas Jefferson University , Philadelphia , PA , USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Fortuna
authors.affiliation: d Department of Pathology , Thomas Jefferson University , Philadelphia , PA , USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Curtis
authors.affiliation: d Department of Pathology , Thomas Jefferson University , Philadelphia , PA , USA.
authors.forename: Zi-Xuan
authors.initials: ZX
authors.lastname: Wang
authors.affiliation: b Perthera, Inc. , McLean , VA , USA.|e Lombardi Comprehensive Cancer Center, Georgetown University Medical Center , Washington , DC , USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pishvaian
authors.affiliation: a Department of Surgery , Jefferson Pancreas, Biliary and Related Cancer Center, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia , PA , USA.
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Winter
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001706:Biopsy; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000037:antagonists & inhibitors / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011725:Pyridines; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C000627630:ivosidenib; D005998:Glycine
keywords: IDH1; IDH1 mutation; multimodal treatment; pancreatic cancer; pancreatic ductal adenocarcinoma; personalized medicine; targeted therapy