Building a national biobank and registry of large and giant congenital melanocytic nevi )

Nevus pointing child The congenital melanocytic nevus (CMN) is a generally sporadic malformation of the skin, due to mutations that take place during pregnancy. The mutant cells spread and proliferate before birth. They then become senescent and give rise to heavily pigmented mosaic regions that can be anywhere on the body. Non-pigmented areas may also be mosaic. We do not know how the scattering and final, somewhat stereotyped distribution patterns of CMN occur.

Large and especially giant CMN, exceeding a predicted diameter at adult age of at least 20 cm, occur once in an estimated 50,000 births. The larger the visible CMN, the rarer, and the more frequently associated with debilitating neuropathology, benign tumors, or with juvenile malignant melanoma, otherwise an exceedingly rare pediatric cancer.

Treatment options for all CMN are exclusively surgical at this time. Given the large and sometimes complex surfaces concerned, surgeries are repeated and therefore disruptive in the lives of growing children and their families. Innovative surgical approaches can cause other complications and at the same time require individual justification to national or private insurance, based more on psychology than on prevention. The systematic collection of diverse biological samples after surgery will be an early, but large step toward understanding the pathophysiology of large/giant CMN and the complications with which they can be associated.

Our research group has obtained all necessary approvals to create a national biobank of skin samples from patients affected with a CMN as well as those who have any resultant melanoma or melanocytic proliferations in the brain. This bank will link biological and clinical findings with the patients' natural and family history. To maintain the biobank, we will enter data in a national registry we are designing with fields that will be interoperable with the international registry project of the Naevus Global patient advocacy federation. We also intend to derive and maintain primary cells when possible for production of induced pluripotent stem (iPS) cell lines.

Our biobank resource will enable the development of cellular and xenograft models that will allow further exploration of the specific aspects of large CMN but also more general principles underlying the mechanistic links between developmental anomalies, cellular senescence and cancer.

The project leader is seeking funding to employ a dedicated clinical research technician for two years, to coordinate data entry and sample processing. This person will also go over all records proposed by French-speaking patient associations in order to boost recruitment for both the national and international registries of this rare malformation. Partial funding will also be applied to the culture reagents necessary to develop and begin to study the iPS cell lines.

France

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  • Milestone 1 - Start-up
    € 15.000
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    Preliminary assessments. Recruitment of the Clinical Research Technician. Familiarization with the database, data entry, meetings with patient association representatives and participating clinical centers.
  • Milestone 2 - First operational phase
    € 7.000
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    Research into archives, recruitment of former patients for inclusion in biobank. Inclusion of 2 prospective families in biobank and corresponding biological sample processing.
  • Milestone 3 - Second operational phase
    € 7.000
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    Recruitment of former patients for inclusion in biobank. Inclusion of 3 prospective families in biobank and corresponding biological sample processing. Preliminary groundwork for derivation of iPS or iNCC lines.
  • Milestone 4 - Third operational phase
    € 7.000
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    Inclusion of 2-3 prospective families in biobank and corresponding biological sample processing and derivation of iPS or iNCC lines.
  • Milestone 5 – Fourth operational phase
    € 7.000
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    Inclusion of 2-3 prospective families in biobank, corresponding biological sample processing, and derivation of iPS or iNCC lines. Functional studies with cell lines in vitro.
  • Milestone 6 - Fifth operational phase
    € 16.000
    Inclusion of 2-3 prospective families in biobank, corresponding biological sample processing, and derivation of iPS or iNCC lines. Functional studies with cell lines in vivo using vertebrate animal models.
  • Milestone 7 - Sixth operational phase
    € 38.500
    Recruitment of 5 or more prospective families in the biobank and corresponding biological sample processing. Derivation of iPS or iNCC lines. Functional studies with cell lines in vivo.
  • Milestone 8 – Seventh operational phase
    € 33.000
    Inclusion of 7 additional families in biobank with corresponding biological sample processing. Functional studies with existing cell lines. Back-up of resources.
  • Milestone 9 – Wrap-up phase
    € 16.500
    Drafting and submission of research paper to peer-reviewed journal for dissemination of results. French- and English-language reports for donors and to the the Naevus Global federation for articulation with the global registry project.