Cancer of Unknown Primary (CUP)

Overview

Cancer of Unknown Primary (CUP) refers to metastatic malignancies in which the anatomic site of origin cannot be definitively identified by standard histopathologic and clinical assessment. On OncoTree it falls under OTHER. CUP represents 2–5% of all cancers and carries a generally poor prognosis.

Cohorts in the corpus

• Included as one of 22 cancer site-of-origin classes in the ATLAS classifier training and validation dataset (TCGA + non-TCGA cohorts). CUP represents a key use case for AI-based tumor-origin classification. PMID:27634761

Recurrent alterations

• No systematic genomic profiling of CUP is reported in the current corpus. ATLAS uses RNA expression rather than mutation profiles for site-of-origin determination.
• MET500 metastatic cohort: carcinoma of unknown primary represented 25/500 (5%) cases; expression-based t-SNE showed metastatic samples including CUP were less well-separated by tissue marker than primary tumors, consistent with dedifferentiation at metastatic sites. PMID:28783718

Subtypes

• ATLAS classifier demonstrated that RNA expression-based predictions for CUP cases can complement pathologic review by providing quantitative lineage and site-of-origin probabilities (22 site classes, 8 lineage classes). High-confidence predictions (score >= 0.99) were 98–99% accurate even in metastatic samples. PMID:27634761

Therapeutic landscape

• AI-based site-of-origin classifiers such as ATLAS can provide actionable tissue-of-origin predictions for CUP patients, enabling site-specific treatment selection and clinical trial enrollment. PMID:27634761

Sources

• PMID:27634761
• PMID:28783718

This page was processed by entity-page-writer on 2026-05-15.