Recent Advances in Studies of Skin Color and Skin Cancer.

The relationship between skin color and skin cancer is well established: the less melanin in one's skin the greater the risk for developing skin cancer. This review is in two parts. First, we summarize the current understanding of the cutaneous pigmentary system and trace melanin from its synthesis in the pigment cell melanosomes through its transfer to keratinocytes.

Leukocyte⁻Cancer Cell Fusion-Genesis of a Deadly Journey.

According to estimates from the International Agency for Research on Cancer, by the year 2030 there will be 22 million new cancer cases and 13 million deaths per year. The main cause of cancer mortality is not the primary tumor itself but metastasis to distant organs and tissues, yet the mechanisms of this process remain poorly understood. Leukocyte⁻cancer cell fusion and hybrid formation as an initiator of metastasis was proposed more than a century ago by the German pathologist Prof.

Sperm cell purification from mock forensic swabs using SOMAmer™ affinity reagents.

We have demonstrated a proof of concept with affinity-based purification of sperm cells from mock forensic samples using SOMAmer™ reagents, DNA-based affinity reagents developed by SomaLogic, Inc. SOMAmer reagents were selected in vitro using whole-cell SELEX to bind specifically with intact, detergent-treated sperm cells. Successful separation of sperm from epithelial cells and their debris was demonstrated using buccal swabs with added semen.

A Melanoma Lymph Node Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: A Second Case of Leucocyte-Tumor Cell Hybridization in Cancer Metastasis.

Background: Metastatic disease is the principal cause of mortality in cancer, yet the underlying mechanisms are not fully understood. Macrophage-cancer cell fusion as a cause of metastasis was proposed more than a century ago by German pathologist Prof. Otto Aichel.

A Melanoma Brain Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: First Evidence for Fusion in Human Cancer.

Background: Tumor cell fusion with motile bone marrow-derived cells (BMDCs) has long been posited as a mechanism for cancer metastasis. While there is much support for this from cell culture and animal studies, it has yet to be confirmed in human cancer, as tumor and marrow-derived cells from the same patient cannot be easily distinguished genetically.

Methods: We carried out genotyping of a metastatic melanoma to the brain that arose following allogeneic bone-marrow transplantation (BMT), using forensic short tandem repeat (STR) length-polymorphisms to distinguish donor and patient genomes.

CTLA4 and generalized vitiligo: two genetic association studies and a meta-analysis of published data.

Several lines of evidence have implicated the gene encoding cytotoxic T lymphocyte antigen 4 (CTLA4) in susceptibility to various autoimmune diseases. However, published studies of genetic association between CTLA4 polymorphisms and vitiligo have yielded conflicting results. Here, we describe two new genetic association studies of CTLA4 single-nucleotide polymorphisms (SNPs) and generalized vitiligo in two independent Romanian Caucasian (CEU) case-control cohorts.

The PTPN22-1858C>T (R620W) functional polymorphism is associated with generalized vitiligo in the Romanian population.

Generalized vitiligo is an autoimmune disorder of the skin in which autoimmune-mediated destruction of melanocytes leads to depigmented patches of skin and overlying hair. The 1858C>T (R620W) functional polymorphism of the PTPN22 gene, which encodes lymphoid protein tyrosine phosphatase (Lyp), has been associated with susceptibility to a number of autoimmune disorders, including generalized vitiligo. The aim of this study was to test genetic association of the PTPN22 1858C>T variant and generalized vitiligo in a Romanian case-control cohort.

PTPN22 is genetically associated with risk of generalized vitiligo, but CTLA4 is not.

Generalized vitiligo is an acquired, multifactorial, polygenic disease in which depigmented spots of skin, overlying hair, and mucus membranes result from autoimmune-mediated loss of melanocytes from affected areas. We examined single-nucleotide polymorphisms (SNPs) in the PTPN22 and CTLA4 genes in 126 Caucasian families with multiple cases of generalized vitiligo and associated autoimmune diseases, using a family-based association study design. The PTPN22 1858T allele of SNP rs2476601 is significantly associated both with generalized vitiligo and with an expanded autoimmunity phenotype.

Separating human DNA mixtures using denaturing high-performance liquid chromatography.

DNA mixtures represent challenging samples that are rarely amenable to direct DNA sequence analysis and many of the strategies available to separate mixtures are both labor and time intensive. Denaturing high-performance liquid chromatography is an accurate and rapid approach for the detection and scoring of mutations. It can also be used to separate DNA mixtures.

Clinical applications of denaturing high-performance liquid chromatography-based genotyping.

Aim: To develop and evaluate heteroduplex forming templates (HFTs) as a common set of molecular standards for genotyping by denaturing high-performance liquid chromatography (DHPLC) using hypervariable regions of human mitochondrial DNA (mtDNA) as a model system.

Methods: Hypervariable regions 1 and 2 from the mtDNA D-loop of 22 maternally related and unrelated human volunteers were amplified by polymerase chain reaction (PCR) and individually mixed with each of three HFTs. Following denaturation and reannealing of the mixture, the resulting hetero- and homoduplicies were separated by DHPLC using temperature-modulated heteroduplex analysis.

Forensic utility of mitochondrial DNA analysis based on denaturing high-performance liquid chromatography.

Aim: To determine the forensic utility for pairwise DNA comparisons and DNA mixture resolution with denaturing high-performance liquid chromatography (DHPLC) of human mitochondrial DNA (mtDNA).

Methods: MtDNA hypervariable regions (HV) 1 and 2 from the mtDNA D-loop were amplified by the polymerase chain reaction and mixed between known and unknown sample sources. The DNA mixtures were denatured and reannealed, and the resultant homo- and heteroduplices were evaluated by temperature-modulated heteroduplex analysis by the DHPLC method.

A genomewide screen for generalized vitiligo: confirmation of AIS1 on chromosome 1p31 and evidence for additional susceptibility loci.

Generalized vitiligo is a common autoimmune disorder characterized by the development of white patches of skin and overlying hair due to loss of pigment-forming melanocytes from the involved areas. Family clustering of cases is not uncommon, in a pattern suggestive of multifactorial, polygenic inheritance, and there is strong association between vitiligo and other autoimmune diseases. To map genetic loci that confer susceptibility to generalized vitiligo and perhaps other autoimmune diseases, we performed a genomewide linkage scan in 71 white multiplex families with vitiligo from North America and the United Kingdom.