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Updated: Jun 2, 2026

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
11:15

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

Genetic mutations in metastatic adenocarcinoma of unknown primary

Hiromi Nagano1, Satoshi Kiyama1, Takayuki Kyutoku1

  • 1Department of Otolaryngology Head and Neck Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

Otolaryngologia Polska = the Polish Otolaryngology
|June 1, 2026
PubMed
Abstract

Insights

Comprehensive genomic profiling (CGP) reveals key mutations in adenocarcinoma of unknown primary (ACUP). GNAS and PIK3CA mutations correlate with better outcomes, while ARID1A and NOTCH1 alterations predict a worse prognosis.

Area of Science:

  • Oncology
  • Genomics
  • Cancer Research

Background:

  • Adenocarcinoma of unknown primary (ACUP) presents diagnostic challenges.
  • Limited established molecularly targeted therapies exist for ACUP.
  • Comprehensive genomic profiling (CGP) is underutilized in ACUP clinical practice.

Purpose of the Study:

  • To elucidate the molecular landscape of ACUP.
  • To determine the prognostic impact of specific genetic mutations in ACUP.
  • To identify potential therapeutic targets in recurrent or metastatic ACUP.

Main Methods:

  • Analysis of somatic mutations in 480 ACUP patients using FoundationOne CDx.
  • Assessment of overall survival (OS) via Kaplan-Meier analysis and Cox proportional hazards modeling.
  • Correlation of specific mutations with patient outcomes.

Main Results:

  • Frequent alterations include TP53 (59.4%), KRAS (31.5%), and CDKN2A (26.3%).
  • GNAS (p=0.046) and PIK3CA (p=0.025) mutations were associated with improved OS.
  • ARID1A (p=0.049) and NOTCH1 (p=0.038) mutations predicted worse OS.

Conclusions:

  • GNAS and PIK3CA mutations indicate a favorable prognosis in ACUP.
  • ARID1A and NOTCH1 alterations are associated with a poor prognosis.
  • Integrating CGP into ACUP management can inform prognostic assessment and treatment strategies.
Keywords:
ARID1ANOTCH1adenocarcinoma of unknown primarycancer genomic profiling testsgenetic mutations

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