In conclusion, we identified brain mitochondrial proteins in p53 null mice that display crucial p53-dependent cellular functions in the central nervous system. Therefore, our results reinforce the concept that the lack of p53 could disturb cell homeostasis causing cells to stimulate defensive pathways. We also elaborated on the link between p53 and mitochondria as we used for the study mitochondria from p53 knock out mice. Since mitochondrial dysfunction is a key feature of neurodegenerative diseases such as AD, p53 conceivably could be a novel therapeutic target for the treatment of these disorders. Molecular features of solid tumours become central in tailoring targeted therapies, but the accessibility to tumour tissue may be sometimes limited due to the size of bioptic samples or the unavailability of biological material, particularly during patients’ follow up. In this context cancer-derived cell-free DNA in blood represents a promising biomarker for cancer diagnosis and an useful surrogate material for molecular characterization. The two classes of alterations detectable in cfDNA from cancer patients include quantitative and qualitative abnormalities. Concerning the former aspect, it is now evident that cancer patients have a higher concentration of cfDNA than healthy individuals. The concentration of cfDNA is influenced by tumor stage, size, location, and other factors. On the other hand, increased plasma DNA level is not a specific cancer marker, as it is observed also in patients with premalignant states, inflammation or trauma. Total cfDNA concentration has been proposed as a marker for early cancer detection, but the studies conducted so far showed a ICI 182780 scarce discriminatory power between patients and controls as well as limited sensitivity and specificity, not allowing one to reach any final conclusion on the diagnostic impact of this parameter. Several studies report a prognostic value of total cfDNA, while conflicting results have been obtained in testing this marker for therapy monitoring. The reduced specificity of this quantitative test leads us to evaluate additional biomarkers reflecting qualitative alterations in cfDNA. A higher specificity in cancer diagnosis can be achieved by detecting tumor specific alterations in cfDNA, such as DNA integrity, genetic and epigenetic modifications. Blood cfDNA in cancer patients originates from apoptotic or necrotic cells. In solid cancers, necrosis generates a spectrum of DNA fragments with variable size, due to random digestion by DNases. In contrast, cell death in normal blood nucleated cells occurs mostly via apoptosis that generates small and uniform DNA fragments. It has generally been observed that in patients affected by several neoplastic diseases plasma DNA contains longer fragments than in healthy subjects reflected by the increase of DNA integrity index. The above mentioned parameters can obviously be considered as non-specific biomarkers, since the increase of cfDNA concentration and integrity is common to the large majority of human solid cancers. When cfDNA is used to detect genetic and epigenetic modifications in a specific tumor, it is necessary to select definite molecular targets that are expected to be altered in affected patients. In cutaneous melanoma, the oncogene BRAF is frequently mutated. BRAF is a serine–threonine protein kinase involved in the RAS–RAF–MEK–ERK pathway which regulates cell growth, survival, differentiation and senescence. The oncogene BRAF is frequently mutated in other human cancers constitutively activating the MAPK pathway. The most common BRAF mutation, which accounts for more than 90% of cases of cancer involving this gene, is the T1799A transversion, converting valine to glutamic acid at position 600.