Pedram Gerami

Guest Editor for the following articles:

Vol. 31. No. 4

Update on the Genetics of Androgenetic Alopecia, Female Pattern Hair Loss, and Alopecia Areata: Implications for Molecular Diagnostic Testing

Pedram Yazdan

Androgenetic alopecia, female pattern hair loss, and alopecia areata are among the most
common forms of nonscarring hair loss encountered in clinical practice. Although the exact
pathogenesis of these forms of alopecia remains to be clarified, genetic factors appear to
have a significant contribution to their pathogenesis. Current treatment strategies are
limited and their effectiveness remains modest at best. This review summarizes the current
purported pathogenesis and recent genetic discoveries relating to these forms of alopecia.
The role of molecular diagnostic testing is also discussed in relation to its future clinical
utility for the prediction of developing hair loss, the diagnosis of the type of alopecia,
prediction of disease severity, development of novel therapeutic and preventative targeted
treatments, as well as determination of response to therapy.
Semin Cutan Med Surg 31:258-266 © 2012 Frontline Medical Communications

Vol. 31. No. 4

Molecular Platforms Utilized to Detect BRAF V600E Mutation in Melanoma

Carlos A. Torres-Cabala, MD | Christopher Bowman, BS, MT(ASCP)SV | Jonathan L. Curry, MD | Michael T. Tetzlaff, MD, PhD | Victor G. Prieto, MD, PhD

Metastatic melanoma (MM) is a deadly skin disease refractory to standard chemotherapy.
Despite numerous clinical and pathological parameters derived to guide patient management,
clinical outcomes in melanoma patients remain difficult to predict. There is a critical
need to delineate the important biomarkers typical of this disease. These biomarkers will
ideally illuminate those key biochemical pathways responsible for the aggressive behavior
of melanoma and, in the process, unveil new opportunities for the design of rational
therapeutic interventions in high-risk patients. The most common recurring mutation in
cutaneous melanoma is the prooncogenic BRAF V600E mutation that drives melanoma cell
proliferation. The development of RAF inhibitors targeted against BRAF V600E mutant
melanoma cells has revolutionized the treatment of MM. Clinical trials with BRAF inhibitor
vemurafenib have shown objective clinical response and improved survival in patients with
MM; therefore, knowledge of the molecular signature of melanoma in patients will be
important in directing management decisions. Several molecular platforms exist to analyze
the mutation status of melanoma. These include Sanger sequencing, pyrosequencing,
allele-specific reverse transcriptase polymerase chain reaction, mass spectrometry base
sequencing (Sequenom), high-resolution melting curve analysis, and next-generation sequencing
methods using microfluidics technology. The Food and Drug Administration has
approved the cobas BRAF V600 Mutation Test developed by Roche to analyze BRAF
mutation status in formalin-fixed paraffin-embedded tumor samples. The cobas Mutation
Test has been designed specifically to detect BRAF V600E mutations, and the analytic
performance of this assay has demonstrated >99% sensitivity in the detection of BRAF
V600E mutation when compared with the Sanger sequencing method and confirmed with
the next-generation sequencing 454-pyrosequencing technology. The lower limit of detection
of the percentage of mutant alleles in a tissue sample for the cobas test is less than
4%-5%. Some cross-reactivity with other variants of mutant BRAF was seen with the cobas
V600 platform; however, this clinical test offers highly sensitive reproducible BRAF V600E
mutation analysis in formalin-fixed paraffin-embedded tumor samples.
Semin Cutan Med Surg 31:267-273 © 2012 Frontline Medical Communications

Vol. 31. No. 4

Molecular Diagnostics for Ambiguous Melanocytic Tumors

Chelsea Cooper, BA | Hilmy Shahbain, BS | Pedram Gerami, MD

Certain subsets of melanocytic neoplasms are difficult to classify because of conflicting histologic
features and the existence of a poorly defined intermediate grade of melanocytic tumors. The
integration of molecular diagnostic information with a histologic impression may contribute significantly
toward improving classification. This review discusses the development of and advances in
molecular techniques, including comparative genomic hybridization and fluorescence in situ hybridization
(FISH) as diagnostic and prognostic tools for melanocytic neoplasms. Further, we
discuss how specific molecular aberrations identified via FISH correlate with certain morphologies
in melanocytic neoplasms. We also examine the prognostic value of FISH in intermediate-grade
melanocytic tumors, particularly atypical Spitz tumors.
Semin Cutan Med Surg 31:274-278 © 2012 Frontline Medical Communications

Vol. 31. No. 4

Molecular Diagnostics in Genodermatoses

Julie V. Schaffer, MD

In recent years, there has been tremendous progress in elucidating the molecular bases of
genodermatoses. The interface between genetics and dermatology has broadened with the
identification of “new” heritable disorders, improved recognition of phenotypic spectrums,
and integration of molecular and clinical data to simplify disease categorization and
highlight relationships between conditions. With the advent of next-generation sequencing
and other technological advances, dermatologists have promising new tools for diagnosis
of genodermatoses. This article first addresses phenotypic characterization and classification
with the use of online databases, considering concepts of clinical and genetic heterogeneity.
Indications for genetic testing related to medical care and patient/family decision
making are discussed. Standard genetic testing is reviewed, including resources for finding
specialized laboratories, methods of gene analysis, and patient/family counseling. The
benefits and challenges associated with multigene panels, array-based analysis (eg, copy
number variation, linkage, and homozygosity), and whole-exome or whole-genome sequencing
are then examined. Specific issues relating to molecular analysis of mosaic skin
conditions and prenatal/preimplantation diagnosis are also presented. Use of the modern
molecular diagnostics described herein enhance our ability to counsel, monitor, and treat
patients and families affected by genodermatoses, with broader benefits of providing
insights into cutaneous physiology and multifactorial skin disorders.
Semin Cutan Med Surg 31:211-220 © 2012 Frontline Medical Communications