New Advances in the Mechanisms and Treatment of Melanoma

**91**

**Chapter 6**

Session

**Abstract**

*and Jekaterina Erenpreisa*

genes are expressed in all three tissue cohorts.

DSB hot spots, ancestral meiosis

**1. Introduction**

The Role of the Meiotic

Component in Reproduction of

*Dace Pjanova, Ninel M. Vainshelbaum, Kristine Salmina* 

The ectopic expression of cancer testis (CT) antigens and classic meiotic genes is characteristic and a hallmark of poor prognosis of melanoma disease. Here the potential mechanisms of meiotic influence on the cell and life cycle of malignant melanoma are reviewed in the genetic, epigenetic, and evolutionary aspects. The involved mutant B-RAF and N-RAS-induced senescence may be reversed by reprogramming, with stemness linked to meiotic landscape, possibly induced by DNA double-strand breaks at the mutual telomere hot spots. The induced by senescence mitotic slippage (reset of interphase from arrested metaphase) and resulting polyploidy trigger the meiotic ploidy cycle to function for effective DNA recombination repair, genome reduction, and escape of survivors, which enter the mitotic cycle again. The aberrant meiotic pathway in cancer is reviewed in the ancestral asexual variants; inverted meiosis is possible. The conundrum of cancer aneuploidy paradox, selection of fit clones, and the Muller's Ratchet of inevitable accumulation of harmful mutations is discussed. The bioinformatic study of the densely connected protein interaction network of CT antigen expressed genes revealed the melanomagenesis attractor composed of PRAME and small MAGEA group in primary tumors as compared with B-RAF-mutant nevi, restructured stemness network; invasive melanoma further displays the leading role of SPANX CT antigen group; meiotic

**Keywords:** B-RAF-mutant melanoma, reversible senescence, reversible polyploidy,

Approximately 50% of melanomas carry mutations in the gene encoding *B-RAF* [1]. Ninety percent of activating *B-RAF* mutations affect the codon 600 and the most common missense change there is V600E [2]. This mutation leads to a constitutive activation of B-RAF, and consequently of the MAPK/ERK pathway,

B-RAF-Mutated Melanoma: A

Review and "Brainstorming"
