ArticlePloS one2012
Novel somatic mutations to PI3K pathway genes in metastatic melanoma.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 98 citations in OpenAlex.
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- Extracellular RNA in melanoma: Advances, challenges, and opportunities.Frontiers in cell and developmental biology · 2023Review
- Therapeutic targeting of anoikis resistance in cutaneous melanoma metastasis.Frontiers in cell and developmental biology · 2023Review
- Prognostic role of IRS-4 in the survival of patients with pancreatic cancer.Histology and histopathology · 2022Article
- Identification of circRNA-miRNA-mRNA Regulatory Network and Crucial Signaling Pathway Axis Involved in Tetralogy of Fallot.Frontiers in genetics · 2022Article
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- Autophagy-Related Long Non-coding RNA Signature as Indicators for the Prognosis of Uveal Melanoma.Frontiers in genetics · 2021Article
- Horizontal Combination of MEK and PI3K/mTOR Inhibition in BRAF Mutant Tumor Cells with or without Concomitant PI3K Pathway Mutations.International journal of molecular sciences · 2020Article
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- BRAF inhibition in melanoma is associated with the dysregulation of histone methylation and histone methyltransferases.Neoplasia (New York, N.Y.) · 2020Article
- Non-BRAF Mutant Melanoma: Molecular Features and Therapeutical Implications.Frontiers in molecular biosciences · 2020Review
- Alteration of tumor associated neutrophils by PIK3CA expression in endometrial carcinoma from TCGA data.Journal of ovarian research · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundBRAF(V600) inhibitors have offered a new gateway for better treatment of metastatic melanoma. However, the overall efficacy of BRAF(V600) inhibitors has been lower than expected in clinical trials, and many patients have shown resistance to the drug's effect. We hypothesized that somatic mutations in the Phosphoinositide 3-Kinase (PI3K) pathway, which promotes proliferation and survival, may coincide with BRAF(V600) mutations and contribute to chemotherapeutic resistance.
methodsWe performed a somatic mutation profiling study using the 454 FLX pyrosequencing platform in order to identify candidate cancer genes within the MAPK and PI3K pathways of melanoma patients. Somatic mutations of theses candidate cancer genes were then confirmed using Sanger sequencing.
resultsAs expected, BRAF(V600) mutations were seen in 51% of the melanomas, whereas NRAS mutations were seen in 19% of the melanomas. However, PI3K pathway mutations, though more heterogeneous, were present in 41% of the melanoma, with PTEN being the highest mutated PI3K gene in melanomas (22%). Interestingly, several novel PI3K pathway mutations were discovered in MTOR, IRS4, PIK3R1, PIK3R4, PIK3R5, and NFKB1. PI3K pathway mutations co-occurred with BRAF(V600) mutations in 17% of the tumors and co-occurred with 9% of NRAS mutant tumors, implying cooperativity between these pathways in terms of melanoma progression.
conclusionsThese novel PI3K pathway somatic mutations could provide alternative survival and proliferative pathways for metastatic melanoma cells. They therefore may be potential chemotherapeutic targets for melanoma patients who exhibit resistance to BRAF(V600) inhibitors.
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