ArticleNeoplasia (New York, N.Y.)2008
Neurofibromin 1 (NF1) defects are common in human ovarian serous carcinomas and co-occur with TP53 mutations.
Article in Neoplasia (New York, N.Y.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 87 citations in OpenAlex.
- In-depth Genetic and Molecular Characterization of Unilateral Coexisting Adrenal Cortical Adenoma and Carcinoma in the Context of MEN1 Syndrome.Endocrine pathology · 2026Article
- Genomic alterations linked to recurrence risk in high-grade serous ovarian cancer revealed by deep targeted sequencing.Scientific reports · 2025Article
- CDK4/6 Inhibitors in Breast Cancer-Who Should Receive Them?International journal of molecular sciences · 2025Review
- Let-7c/RUNX1 Axis Promotes Cervical Cancer: A Bioinformatic Analysis.Current issues in molecular biology · 2025Article
- Clinicopathologic Characteristics and Prognostic Profile of Chronic Myeloid Neoplasms With Somatic NF1 Mutations in Adult Patients.European journal of haematology · 2025Article
- Biological characteristics of spontaneous ovarian cancer inZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- Genomic Alterations Correlated to Trastuzumab Resistance and Clinical Outcomes in HER2+/HR- Breast Cancers of Patients Living in Northwestern China.Journal of Cancer · 2024Article
- RAS Signaling Gone Awry in the Skin: The Complex Role of RAS in Cutaneous Neurofibroma Pathogenesis, Emerging Biological Insights.The Journal of investigative dermatology · 2023Review
- Proteogenomic Approaches for the Identification of NF1/Neurofibromin-depleted Estrogen Receptor-positive Breast Cancers for Targeted Treatment.Cancer research communications · 2023Article
- Exploring the tumor micro-environment in primary and metastatic tumors of different ovarian cancer histotypes.Frontiers in cell and developmental biology · 2023Article
- Review
- ALPK2 acts as tumor promotor in development of bladder cancer through targeting DEPDC1A.Cell death & disease · 2021Article
- Clinical perspectives of BET inhibition in ovarian cancer.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Review
- Biallelic NF1 inactivation in high grade serous ovarian cancers from patients with neurofibromatosis type 1.Familial cancer · 2020Article
- Trametinib response in heavily pretreated high-grade ovarian cancer: One step towards precision medicine.Gynecologic oncology reports · 2020Article
- Knockdown of ALPK2 inhibits the development and progression of Ovarian Cancer.Cancer cell international · 2020Article
- Intrinsic Resistance to MEK Inhibition through BET Protein-Mediated Kinome Reprogramming in NF1-Deficient Ovarian Cancer.Molecular cancer research : MCR · 2019Article
- Ras-Specific GTPase-Activating Proteins-Structures, Mechanisms, and Interactions.Cold Spring Harbor perspectives in medicine · 2019Review
- Neurofibromin 1 expression is negatively correlated with malignancy and prognosis of epithelial ovarian cancer.International journal of clinical and experimental pathology · 2019Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Ovarian serous carcinoma (OSC) is the most common and lethal histologic type of ovarian epithelial malignancy. Mutations of TP53 and dysfunction of the Brca1 and/or Brca2 tumor-suppressor proteins have been implicated in the molecular pathogenesis of a large fraction of OSCs, but frequent somatic mutations in other well-established tumor-suppressor genes have not been identified. Using a genome-wide screen of DNA copy number alterations in 36 primary OSCs, we identified two tumors with apparent homozygous deletions of the NF1 gene. Subsequently, 18 ovarian carcinoma-derived cell lines and 41 primary OSCs were evaluated for NF1 alterations. Markedly reduced or absent expression of Nf1 protein was observed in 6 of the 18 cell lines, and using the protein truncation test and sequencing of cDNA and genomic DNA, NF1 mutations resulting in deletion of exons and/or aberrant splicing of NF1 transcripts were detected in 5 of the 6 cell lines with loss of NF1 expression. Similarly, NF1 alterations including homozygous deletions and splicing mutations were identified in 9 (22%) of 41 primary OSCs. As expected, tumors and cell lines with NF1 defects lacked mutations in KRAS or BRAF but showed Ras pathway activation based on immunohistochemical detection of phosphorylated MAPK (primary tumors) or increased levels of GTP-bound Ras (cell lines). The TP53 tumor-suppressor gene was mutated in all OSCs with documented NF1 mutation, suggesting that the pathways regulated by these two tumor-suppressor proteins often cooperate in the development of ovarian carcinomas with serous differentiation.
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