Related Experiment Video

Updated: Apr 18, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

6.6K

Activating PIK3CA mutations coexist with BRAF or NRAS mutations in a limited fraction of melanomas

Antonella Manca, Amelia Lissia, Mariaelena Capone

  • 1Institute of Biomolecular Chemistry, National Research Council (CNR), Traversa La Crucca 3 - Baldinca Li Punti, Sassari, 07100, Italy. gpalmieri@yahoo.com.

Journal of Translational Medicine
|January 29, 2015
PubMed
Abstract

Insights

PIK3CA mutations are uncommon in melanoma and rarely co-occur with BRAF/NRAS mutations. Their presence shows a limited impact on drug resistance in melanoma treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The PI3K-AKT pathway is crucial in melanoma pathogenesis and can lead to resistance against targeted therapies.
  • While BRAF, NRAS, and MEK are key effectors, PIK3CA mutations are less frequently implicated in PI3K-AKT pathway activation.

Purpose of the Study:

  • To determine the prevalence of coexisting BRAF/NRAS and PIK3CA mutations in melanoma.
  • To investigate the functional impact of PIK3CA mutations on treatment response in melanoma.

Main Methods:

  • Screening of 245 melanoma specimens (primary tumors and cell lines) for BRAF, NRAS, and PIK3CA mutations using automated direct sequencing.
  • Assessing the effect of PIK3CA mutations on vemurafenib sensitivity in melanoma cell lines with BRAF mutations.

Main Results:

  • BRAF mutations were found in 44.9%, NRAS in 10.6%, and PIK3CA in 9.8% of samples.
  • Coexistence of PIK3CA with BRAF/NRAS mutations was observed in 4.9% of cases.
  • Melanoma cells with both BRAF and PIK3CA mutations exhibited reduced sensitivity to vemurafenib compared to those with BRAF mutations alone.

Conclusions:

  • PIK3CA mutations represent a minor contributor to PI3K pathway activation in melanoma.
  • PIK3CA mutations have a limited role in mediating resistance to BRAF/NRAS-driven melanoma growth.

More Related Videos

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

9.7K
Author Spotlight: Integrating BRET-Based Assays and Rare Mutation Analysis to Decipher RAF Kinase Regulation in Live Cells06:44

Author Spotlight: Integrating BRET-Based Assays and Rare Mutation Analysis to Decipher RAF Kinase Regulation in Live Cells

Published on: March 1, 2024

1.9K

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
7.6K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.5K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
8.0K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.5K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.1K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.5K