Related Experiment Video

Updated: Sep 2, 2025

An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
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Comprehensive genomic and epigenomic analysis in cancer of unknown primary guides molecularly-informed therapies

Lino Möhrmann1,2,3, Maximilian Werner1, Małgorzata Oleś4,5

  • 1Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Nature Communications
|August 2, 2022
PubMed

Insights

Molecular profiling of cancer of unknown primary (CUP) reveals genetic diversity and aids in identifying potential treatments. Genomics-based recommendations show promise in improving progression-free survival for CUP patients.

Area of Science:

  • Oncology
  • Genomics
  • Cancer Biology

Background:

  • Cancer of unknown primary (CUP) presents a diagnostic and therapeutic challenge.
  • The efficacy of molecularly-guided therapies in CUP remains largely undefined.

Purpose of the Study:

  • To comprehensively characterize the molecular landscape of CUP.
  • To assess the clinical utility of molecular profiling for treatment selection in CUP patients.

Main Methods:

  • Whole genome/exome, transcriptome, and methylome analyses were performed on 70 CUP patient samples.
  • Genomic alterations, gene fusions, and homozygous deletions were identified.
  • Germline analysis was conducted to detect pathogenic mutations.

Main Results:

  • Significant mutational heterogeneity was observed, with TP53, MUC16, KRAS, LRP1B, and CSMD3 as frequently mutated genes.
  • FGFR2 was the most common fusion partner, and CDKN2A the most common homozygous deletion.
  • Molecular data aided in identifying the underlying cancer entity in 89% of cases.
  • Genomics-based treatment recommendations were provided to 80% of patients, with 36% receiving them.
  • Off-label therapies based on recommendations improved progression-free survival (PFS ratio of 3.6).

Conclusions:

  • Comprehensive molecular profiling is clinically valuable for CUP patients.
  • Molecular data can help determine the tissue of origin in most CUP cases.
  • Mechanism-based clinical trials are essential for advancing CUP treatment.

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