UVB-induced apoptosis drives clonal expansion during skin tumor development.

The mechanism by which a single mutant cell clonally expands is usually assumed to involve an additional mutation in a cell cycle regulatory gene. An alternative mechanism for driving clonal expansion is apoptosis, which might create vacant stem cell compartments that can be repopulated by mutant cells. This model predicts that in a mouse with reduced apoptotic capacity (i) more mutated cells will appear initially but (ii) these cells will expand into clones more slowly than in wild-type animals.

Vulvar melanoma: diffuse melanosis and metastasis to the placenta.

Mucocutaneous melanoma, including vulvar melanoma, is rare and has a worse prognosis and higher recurrence rate than traditional cutaneous melanoma. Diffuse cutaneous melanosis is another rare clinical presentation of metastatic melanoma. It is essential for dermatologists to be alerted to rare presentations of melanoma, to facilitate early detection.

Pancreatic carcinoma surveillance in patients with familial melanoma.

Objective: To determine the optimal methods for pancreatic adenocarcinoma surveillance in high-risk patients with familial melanoma and cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations.

Design: Case report with pedigree analysis and literature review, with an emphasis on guideline development for high-risk kindreds with familial pancreatic adenocarcinoma.

Setting: A university-affiliated familial melanoma research clinic.

Metastatic melanoma in pregnancy: risk of transplacental metastases in the infant.

Purpose: Although metastases to the fetus via the placenta are rare, melanoma is the most common culprit. When it occurs, maternally derived melanoma metastasis in the infant is almost invariably fatal.

Patients And Methods: This article reviews current guidelines for placental evaluation in pregnant women with metastatic melanoma and presents surveillance recommendations for their infants.

Survivin expression in mouse skin prevents papilloma regression and promotes chemical-induced tumor progression.

Induction of cutaneous squamous cell carcinoma (SCC) in mice, by topical chemical [9,10-dimethylbenzanthracene (DMBA) and phorbol 12-myristate 13-acetate (PMA)] application, is a multistep process involving papilloma formation and progression to carcinoma. We have generated a transgenic (Tg) mouse [keratin-14 (K14)-survivin] with skin expression of survivin, an inhibitor of apoptosis expressed in most human skin cancers and premalignant lesions. K14-survivin mice were resistant to DMBA-induced keratinocyte apoptosis.

Apoptosis regulators and responses in human melanocytic and keratinocytic cells.

Apoptosis in keratinocytes is required for epidermal turnover, stratum corneum formation, and removal of ultraviolet-damaged premalignant cells. Its role in melanocyte homeostasis and transformation, on the other hand, has not been defined, although apoptosis resistance is a commonly recognized feature of melanoma. We examined the expression of apoptosis regulators in melanocytes, keratinocytes, melanoma, and HaCat cells.