Study to Test Genetic Alterations Among Different Dermoscopic Types of Melanocytic Nevi.

• Sponsor: Medical University of Graz (Other)
• Overall Status: Completed
• CT.gov ID: NCT00422448
• Collaborator: (none)
• Enrollment: 43
• Location: 1
• Arm: 1
• Duration (Months): 43
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This project is a multicenter study in which we will investigate a dual concept of nevogenesis. Study location is the Department of Dermatology at the Medical University of Graz in collaboration with centers in Austria (Vienna), Italy (Naples, Benevento, Modena), Spain (Barcelona) and the United States (New York).

The hypothesis is that small congenital melanocytic nevi (CMN), "early" acquired melanocytic nevi in childhood (AMN) and dermal nevi, all dermatoscopically characterized by globular pattern, belong to the same spectrum of genetically determined melanocytic proliferations that develop due to endogenous pathways, in contrast to "true" acquired melanocytic nevi, dermatoscopically showing reticular pattern, that develop due to exogeneous factors such as UV-exposure.

Condition or Disease	Intervention/Treatment	Phase
Nevi	Genetic: To test the frequency of BRAF and NRAS mutations among nevi	N/A

Detailed Description

The investigations to this study will verify whether small CMN, "early" AMN and dermal nevi, characterized by globular pattern differ in their genetic alterations compared to reticular typed nevi. It will be expected that globular typed nevi and eventually dermal nevi lack

B-RAF mutations whereas reticular nevi show alterations in the B-RAF gene. Study location:

Graz

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: BRAF and Nevi.Nevi Are Common Benign Pigmented Tumors of the Skin. Mutations in So-called BRAF and NRAS Genes Genes Appear to be Initiating Events Responsible for the Formation of Nevi.
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nevi from participants Benign nevi dermoscopically sub-classified into 4 dermoscopic types (i.e., with globular, reticular, mixed pattern with globules in the center and mixed pattern with globules at the periphery) were excised from healthy volunteers for further genetical analysis	Genetic: To test the frequency of BRAF and NRAS mutations among nevi; Benign nevi excised for the study purpose where genetically analyzed for the presence/absence of BRAF and NRAS mutations; Other Names: NM_004333; Homo sapiens v-raf murine sarcoma viral oncogene homolog B1

Outcome Measures

Primary Outcome Measures

1. Frequency of BRAF Mutations Among Nevi [up to 30 months]

   All nevi were analyzed for BRAF mutations using the (less sensitive) Sanger method. A random subset of nevi was also analyzed using the (more sensitive) Ultradeep pyro-sequencing method (UDPS). The frequency is reported here as the number of BRAF mutations found by each method.

Secondary Outcome Measures

1. Frequency of NRAS Mutations Among Nevi [30 months]

   All nevi were analyzed for NRAS mutations using the (less sensitive) Sanger method. The (more sensitive) Ultradeep pyro-sequencing method (UDPS) is not applicable for this mutation. The frequency is reported here as the number of NRAS mutations from the analyzed nevi.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 9 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy individuals aged 9 to 80 years showing one or more dermoscopically benign nevi with either uniform globular-cobblestone pattern or reticular pattern or a combination of both types

Exclusion Criteria:

• Children under the age of 9 years

• Pregnant woman

• Patients with atypical nevi (i.e., melanoma cannot be clinically ruled out)

• Patients with immunosuppression

• Patients with sun exposure 4 weeks before enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Dermatology, Medical University of Graz	Graz		Austria	8036

Sponsors and Collaborators

• Medical University of Graz

Investigators

• Study Chair: Iris Zalaudek, MD, Department of Dermatology, Medical University of Graz

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Webpage of the sponsoring organization

Publications

• Zalaudek I, Grinschgl S, Argenziano G, Marghoob AA, Blum A, Richtig E, Wolf IH, Fink-Puches R, Kerl H, Soyer HP, Hofmann-Wellenhof R. Age-related prevalence of dermoscopy patterns in acquired melanocytic naevi. Br J Dermatol. 2006 Feb;154(2):299-304.
• Zalaudek I, Hofmann-Wellenhof R, Soyer HP, Ferrara G, Argenziano G. Naevogenesis: new thoughts based on dermoscopy. Br J Dermatol. 2006 Apr;154(4):793-4.

• ClinicalTrials.gov Identifier: NCT00422448
• Other Study ID Numbers: V9-B05 (FWF)
• First Posted: Jan 17, 2007
• Last Update Posted: Jan 14, 2011
• Last Verified: Dec 1, 2010

• Keywords provided by , ,: Dermoscopy; Histopathology; Genetics; Nevi; Nevogenesis
• Additional relevant MeSH terms: Nevus

Study Results

Participant Flow

Recruitment Details	Pigmented lesion clinic from October 2006 to March 2009
Pre-assignment Detail	Insufficient prospective accrual of patients during the 1st year of enrollment lead to additional retrospective inclusion of a dataset of 21 paraffin-embedded tissue specimens from excised nevi .

Arm/Group Title	Nevi
Arm/Group Description	with or without BRAF and NRAS
Period Title: Overall Study
STARTED	43
COMPLETED	43
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Nevi
Arm/Group Description	with or without BRAF and NRAS
Overall Participants	43
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	43 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.3 (9.413)
Sex: Female, Male (Count of Participants)
Female	23 53.5%
Male	20 46.5%
Region of Enrollment (participants) [Number]
Austria	22 51.2%
Italy	21 48.8%

Outcome Measures

1. Primary Outcome

Title	Frequency of BRAF Mutations Among Nevi
Description	All nevi were analyzed for BRAF mutations using the (less sensitive) Sanger method. A random subset of nevi was also analyzed using the (more sensitive) Ultradeep pyro-sequencing method (UDPS). The frequency is reported here as the number of BRAF mutations found by each method.
Time Frame	up to 30 months

Outcome Measure Data

Analysis Population Description

All nevi were analyzed for BRAF mutations using the (less sensitive) Sanger method. A random subset of nevi was also analyzed using the (more sensitive) Ultradeep pyro-sequencing method (UDPS). The frequency is reported here as the number of BRAF mutations found by each method.

Arm/Group Title	Nevi
Arm/Group Description	with or without BRAF and NRAS
Measure Participants	43
Measure nevi	45
Sanger method (n=45)	6
UDPS (n=24)	19

2. Secondary Outcome

Title	Frequency of NRAS Mutations Among Nevi
Description	All nevi were analyzed for NRAS mutations using the (less sensitive) Sanger method. The (more sensitive) Ultradeep pyro-sequencing method (UDPS) is not applicable for this mutation. The frequency is reported here as the number of NRAS mutations from the analyzed nevi.
Time Frame	30 months

Outcome Measure Data

Analysis Population Description

All nevi were analyzed for NRAS mutations using the (less sensitive) Sanger method. The (more sensitive) Ultradeep pyro-sequencing method (UDPS) is not applicable for this mutation. The frequency is reported here as the number of NRAS mutations from the analyzed nevi.

Arm/Group Title	Nevi
Arm/Group Description	with or without BRAF and NRAS
Measure Participants	43
Measure number of nevi	45
Number [NRAS mutations]	0

Adverse Events

Time Frame	were not collected or assessed
Adverse Event Reporting Description	postoperative complications were not collected or assessed
Arm/Group Title	Nevi
Arm/Group Description	with or without BRAF and NRAS
All Cause Mortality
	Nevi
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Nevi
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Nevi
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

During first year of enrollment too few patients agreed to participate. Therefore a sample of 21 nevi were additionally retrospectively included.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.