ArticleOncotarget2016
Molecular driver alterations and their clinical relevance in cancer of unknown primary site.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- SEOM-GECOD clinical guideline for cancer of unknown primary (update 2025).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Guideline
- SEOM-GECOD clinical guideline for unknown primary cancer (2021).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Guideline
- The Quest for Improving Treatment of Cancer of Unknown Primary (CUP) Through Molecularly-Driven Treatments: A Systematic Review.Frontiers in oncology · 2020Pooled it
- Nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary: a phase II trial.Nature communications · 2023Trial
- A prospective national precision medicine trial evaluating the feasibility of blood-based molecular profiling in patients with Cancer of Unknown Primary (CUP-COMP).British journal of cancer · 2026Article
- Cancer of unknown primary: the evolution of tissue of origin identification in the artificial intelligence era.Biomarker research · 2026Review
- Epidemiologic, histopathological, and prognostic analysis of cancer of unknown primary in an Iranian population.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2025Article
- A machine learning-based method for feature reduction of methylation data for the classification of cancer tissue origin.International journal of clinical oncology · 2024Article
- Biomarkers of systemic inflammation provide additional prognostic stratification in cancers of unknown primary.Cancer medicine · 2024Article
- Article
- Histopathological Evaluation and Molecular Diagnostic Tests for Peritoneal Metastases with Unknown Primary Site-a Review.Indian journal of surgical oncology · 2023Review
- Mutated axon guidance gene PLXNB2 sustains growth and invasiveness of stem cells isolated from cancers of unknown primary.EMBO molecular medicine · 2023Article
- A comparison of DNA sequencing and gene expression profiling to assist tissue of origin diagnosis in cancer of unknown primary.The Journal of pathology · 2023Article
- Comprehensive genomic and epigenomic analysis in cancer of unknown primary guides molecularly-informed therapies despite heterogeneity.Nature communications · 2022Article
- Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP).Scientific reports · 2021Article
- Cancer of Unknown Primary in the Molecular Era.Trends in cancer · 2021Review
- Review
- Progress in refining the clinical management of cancer of unknown primary in the molecular era.Nature reviews. Clinical oncology · 2020Review
- Cancer of Unknown Primary (CUP): genetic evidence for a novel nosological entity? A case report.EMBO molecular medicine · 2020Article
- "Metastatic Cancer of Unknown Primary" or "Primary Metastatic Cancer"?Frontiers in oncology · 2019Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer of unknown primary (CUP) is defined as metastatic solid malignancy where no primary tumor is detected despite appropriate staging. About 90% of CUP represent adenocarcinoma or undifferentiated carcinoma. Since therapy regimens are only modestly effective, identification of the molecular landscape of these neoplasms might be a promising approach to direct CUP therapy and aid in tumor classification. We screened a cohort of 128 patients with adenocarcinoma or undifferentiated carcinoma meeting the definition of CUP. Massive parallel multigene sequencing of 50 genes, which had been selected due to their relevance as oncogenic drivers or druggable molecular targets could ultimately be performed on samples from 55 patients for whom complete clinical datasets were also available. Overall, 60 tumor-specific mutations and 29 amplifications/deletions, as revealed by coverage analysis, were detected in 46 cases (84%). The most frequently mutated genes were TP53 (30 cases, 55%), KRAS (9 cases, 16%), CDKN2A (5 cases, 9%), and SMAD4 (5 cases, 9%). The most frequently deleted gene was CDKN2A (8 cases, 15%). KRAS and CDKN2A mutations significantly correlated with poor progression-free survival (PFS) and, in case of KRAS, overall survival (OS). WIldtype TP53 and female sex defined a relatively favorable category, with favorable PFS and OS. 8 cases (15%) harbored mutations that may be targetable by currently approved drugs. Taken together, Mutations of relevant driver genes are present in the vast majority of CUP tumors. Some of them impact on prognosis and a subset is putatively druggable.
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