ArticleJournal of hematology & oncology2015
Comprehensive serial molecular profiling of an "N of 1" exceptional non-responder with metastatic prostate cancer progressing to small cell carcinoma on treatment.
Article in Journal of hematology & oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Whole-exome sequencing unveils novel potential gene mutations involved in primary renal small cell carcinoma.Oncology letters · 2026Article
- Mechanistic insights and molecular therapy for neuroendocrine prostate cancer.Frontiers in oncology · 2026Review
- Imaging of Neuroendocrine Prostatic Carcinoma.Cancers · 2021Review
- Case Report: Systemic Treatment and Serial Genomic Sequencing of Metastatic Prostate Adenocarcinoma Progressing to Small Cell Carcinoma.Frontiers in oncology · 2021Article
- Immune molecular profiling of a multiresistant primary prostate cancer with a neuroendocrine-like phenotype: a case report.BMC urology · 2020Article
- Systems Biology of Cancer Metastasis.Cell systems · 2019Review
- Tubulocystic renal cell carcinoma: a distinct clinicopathologic entity with a characteristic genomic profile.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2019Article
- A gastric MANEC with an adenocarcinoma of fundic-gland type as exocrine component.Virchows Archiv : an international journal of pathology · 2017Article
- Molecular Profiling of Multiple Primary Merkel Cell Carcinoma to Distinguish Genetically Distinct Tumors From Clonally Related Metastases.JAMA dermatology · 2017Article
- Strategies to avoid treatment-induced lineage crisis in advanced prostate cancer.Nature reviews. Clinical oncology · 2017Review
- Targeted next-generation sequencing of CIC-DUX4 soft tissue sarcomas demonstrates low mutational burden and recurrent chromosome 1p loss.Human pathology · 2016Article
- Tubulocystic Carcinoma of the Kidney With Poorly Differentiated Foci: A Frequent Morphologic Pattern of Fumarate Hydratase-deficient Renal Cell Carcinoma.The American journal of surgical pathology · 2016Article
- Translational and clinical implications of the genetic landscape of prostate cancer.Nature reviews. Clinical oncology · 2016Review
- Neuroendocrine Tumors of the Prostate: Emerging Insights from Molecular Data and Updates to the 2016 World Health Organization Classification.Endocrine pathology · 2016Review
- Article
- The Role of Next-Generation Sequencing in Castration-Resistant Prostate Cancer Treatment.Cancer journal (Sudbury, Mass.)Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
importanceSmall cell carcinoma/neuroendocrine prostate cancer (NePC) is a lethal, poorly understood prostate cancer (PCa) subtype. Controversy exists about the origin of NePC in this setting.
objectiveTo molecularly profile archived biopsy specimens from a case of early-onset PCa that rapidly progressed to NePC to identify drivers of the aggressive course and mechanisms of NePC origin and progression. DESIGN, SETTING, AND
participantsA 47-year-old patient presented with metastatic prostatic adenocarcinoma (Gleason score 9). After a 6-month response to androgen deprivation therapy, the patient developed jaundice and liver biopsy revealed exclusively NePC. Targeted next generation sequencing (NGS) from formalin-fixed paraffin-embedded (FFPE)-isolated DNA was performed from the diagnostic prostate biopsy and the liver biopsy at progression.
interventionAndrogen deprivation therapy for adenocarcinoma followed by multiagent chemotherapy for NePC. MAIN OUTCOMES AND MEASURES: Identification of the mutational landscape in primary adenocarcinoma and NePC liver metastasis. Whether the NePC arose independently or was derived from the primary adenocarcinoma was considered based on mutational profiles.
resultsA deleterious somatic SMAD4 L535fs variant was present in both prostate and liver specimens; however, a TP53 R282W mutation was exclusively enriched in the liver specimen. Copy number analysis identified concordant, low-level alterations in both specimens, with focal MYCL amplification and homozygous PTEN, RB1, and MAP2K4 losses identified exclusively in the NePC specimen. Integration with published genomic profiles identified MYCL as a recurrently amplified in NePC. CONCLUSIONS AND RELEVANCE: NGS of routine biopsy samples from an exceptional non-responder identified SMAD4 as a driver of the aggressive course and supports derivation of NePC from primary adenocarcinoma (transdifferentiation).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.