ArticleMolecular carcinogenesis2019
Inter- and intra-tumor heterogeneity of SMAD4 loss in head and neck squamous cell carcinomas.
Article in Molecular carcinogenesis, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Single-Cell RNA Sequencing Reveals the Heterogeneity and Microenvironment of Temporal Bone Squamous Cell Carcinoma.Clinical and experimental otorhinolaryngology · 2026Article
- Interaction of the tumor suppressor SMAD4 and WNT signaling in progression to oral squamous cell carcinoma.The Journal of pathology · 2024Article
- Preclinical models in head and neck squamous cell carcinoma.British journal of cancer · 2023Review
- The Role of Inflammation-Associated Factors in Head and Neck Squamous Cell Carcinoma.Journal of inflammation research · 2023Review
- A RAS-Independent Biomarker Panel to Reliably Predict Response to MEK Inhibition in Colorectal Cancer.Cancers · 2022Article
- Serum-derived extracellular vesicles mediate Smad4 expression through shuttling microRNA-27a in the progression of laryngeal squamous cell carcinoma.Human cell · 2022Article
- Setting up clinical trials for success: Applying preclinical advances in combined TGFβ/PD-L1 inhibition to ongoing clinical studies.Molecular carcinogenesis · 2022Article
- Why responses to immune checkpoint inhibitors are heterogeneous in head and neck cancers: Contributions from tumor-intrinsic and host-intrinsic factors.Frontiers in oncology · 2022Review
- Distinct immune microenvironment profiles of therapeutic responders emerge in combined TGFβ/PD-L1 blockade-treated squamous cell carcinoma.Communications biology · 2021Article
- Review
- Recent advancements in PARP inhibitors-based targeted cancer therapy.Precision clinical medicine · 2020Review
- The role of transforming growth factor-beta in immune suppression and chronic inflammation of squamous cell carcinomas.Molecular carcinogenesis · 2020Review
- PARP Inhibition Enhances Radiotherapy of SMAD4-Deficient Human Head and Neck Squamous Cell Carcinomas in Experimental Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Preclinical models of head and neck squamous cell carcinoma for a basic understanding of cancer biology and its translation into efficient therapies.Cancers of the head & neck · 2020Review
- Lessons learned from SMAD4 loss in squamous cell carcinomas.Molecular carcinogenesis · 2019Review
- Macrophages Promote Growth of Squamous Cancer Independent of T cells.Journal of dental research · 2019Article
- Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Reports regarding the frequency of SMAD4 loss in human head and neck squamous cell carcinoma (HNSCC) vary significantly. We have shown that SMAD4 deletion contributes to HNSCC initiation and progression. Therefore, accurately detecting genetic SMAD4 loss is critical to determine prognosis and therapeutic interventions in personalized medicine. We developed a SMAD4 fluorescence in situ hybridization (FISH) assay to identify chromosomal SMAD4 loss at the single cell level of primary HNSCC specimens and patient derived xenograft (PDX) tumors derived from HNSCCs. SMAD4 heterozygous loss was detected in 35% of primary HNSCCs and 41.3% of PDX tumors. Additionally, 4.3% of PDX tumors had SMAD4 homozygous loss. These frequencies of SMAD4 loss were similar to those in The Cancer Genome Atlas (TCGA). However, we identified significant heterogeneities of SMAD4 loss (partial or complete) among cells within each tumor. We also found that aneuploidy (monosomy and polysomy) contributed greatly to how to define chromosomal SMAD4 deletion. Furthermore, in cultured PDX tumors, SMAD4 mutant cells outcompeted SMAD4 wildtype cells, resulting in establishing homogenous SMAD4 mutant HNSCC cell lines with partial or complete genomic SMAD4 loss, suggesting a survival advantage of SMAD4 mutant cells. Taken together, our study reveals inter- and intra-tumor heterogeneities of SMAD4 chromosomal loss in HNSCCs. Further, SMAD4 FISH assay provides a platform for future clinical diagnosis of SMAD4 chromosomal loss that potentially serves as a molecular marker for prognosis and therapeutic intervention in cancer patients.
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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.