Genes frequently altered in pancreatic neuroendocrine tumors

Patent metadata

Field	Value
Publication number	US-2019055610-A1
Application number	US-201816179136-A
Country	US
Kind code	A1
Filing date	Nov 2, 2018
Priority date	Jan 4, 2011
Publication date	Feb 21, 2019
Grant date	—

Abstract

Pancreatic Neuroendocrine Tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia. To explore the genetic basis of PanNETs, we determined the exomic sequences of ten non-familial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. Remarkably, the most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN-1, which encodes menin, a component of a histone methyltransferase complex; and 43% had mutations in genes encoding either of the two subunits of a transcription/chromatin remodeling complex consisting of DAXX (death-domain associated protein) and ATRX (alpha thalassemia/mental retardation syndrome X-linked). Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with better prognosis. We also found mutations in genes in the mTOR (mammalian target of rapamycin) pathway in 14% of the tumors, a finding that could potentially be used to stratify patients for treatment with mTOR inhibitors.

First claim

We claim:

1 . A method for predicting outcome of a pancreatic neuroendocrine tumor in a patient, comprising:
testing the pancreatic neuroendocrine tumor, or cells or nucleic acids shed from the tumor, for the presence of an inactivating mutation in MEN1, DAXX, or ATRX, wherein a mutation in at least one of these genes is a positive prognostic indicator.

Assignees

• Univ Johns Hopkins

Inventors

• Vogelstein Bert
• Kinzler Kenneth W
• Velculescu Victor
• Diaz Luis
• Papadopoulos Nickolas
• Jiao Yuchen
• Hruban Ralph

Classifications

• G01N33/57525

  of the liver or pancreas · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• C12Q2600/118

  Prognosis of disease development · CPC title

• C12Q2600/112

  Disease subtyping, staging or classification · CPC title