Related Experiment Video

Updated: Aug 25, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

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

Published on: June 7, 2019

Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma

Hensin Tsao1, Vikas Goel, Heng Wu

  • 1Wellman Laboratories, Department of Dermatology, Massachusetts General Hospital Melanoma Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

The Journal of Investigative Dermatology
|March 11, 2004
PubMed

Insights

Activating mutations in BRAF and loss of PTEN may cooperate to drive melanoma development. This study found frequent co-occurrence of these genetic alterations in melanoma cell lines and metastases.

Area of Science:

  • Oncology
  • Genetics
  • Dermatology

Background:

  • Growth factor signaling pathways are implicated in cutaneous melanoma pathogenesis.
  • Reciprocal activating mutations in NRAS and BRAF have been identified in melanoma.
  • Previous research indicated an epistatic relationship between NRAS mutations and PTEN/MMAC1 alterations.

Purpose of the Study:

  • To investigate the potential cooperative role of BRAF and PTEN/MMAC1 mutations in melanoma tumorigenesis.
  • To determine the frequency of NRAS, BRAF, and PTEN/MMAC1 mutations in melanoma cell lines and metastases.

Main Methods:

  • Analysis of mutation status for NRAS, BRAF, and PTEN/MMAC1 in 47 melanoma cell lines and 16 melanoma metastases.
  • Genotyping of melanoma samples to identify specific mutations and alterations.

Main Results:

  • Mutations in NRAS, BRAF, or PTEN/MMAC1 were present in 85% of cell lines and 69% of metastases.
  • BRAF mutations were found in 60% of cell lines and 56% of metastases, while NRAS mutations were less frequent.
  • PTEN alterations were frequently associated with BRAF mutations, observed in 80% of cell lines and 100% of metastases with PTEN alterations.

Conclusions:

  • The findings suggest a cooperative interaction between BRAF activation and PTEN loss in promoting melanoma development.
  • These genetic alterations represent key events in melanoma tumorigenesis.

More Related Videos

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

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

Published on: July 17, 2019

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma08:18

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma

Published on: September 8, 2021

Related Concept Videos

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...
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 superfamily...
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...
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 rapamycin-insensitive companion...
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...
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 daughter...