Abstract Introduction Serial monitoring for disease progression and therapeutic efficacy at the molecular level in metastatic melanoma is hampered by a lack of reliable blood borne biomarkers. Molecular profiling tumours almost impractical due to risks procedure related morbidity sampling inefficiency representing tumour heterogeneity. Cell free DNA allows changes over course immunotherapy. We ...

Germline mutations are the principal cause of heritable disease and the ultimate source of evolutionary change. Similarly, somatic mutations are the primary cause of cancer and may contribute to the burden of human disease more broadly than previously appreciated. Here, we review recent insights into the rates, spectrum, and determinants of genomic mutations and how these parameters inform our ...

Recent experiments have strongly suggested that the process of somatic mutation is linked to transcription initiation. It was postulated that a mutator factor loads onto the RNA polymerase and, during elongation, causes transcriptional arrest that activates DNA repair, thus occasionally causing errors in the DNA sequence. We report the analysis of the role of one of the known DNA repair systems...

BACKGROUND The purpose of this study was to characterize somatic mutations in the D-loop of mitochondrial DNA (mtDNA) and their impact on survival in patients with head and neck cancer. METHODS Histologically confirmed head and neck cancer and corresponding noncancerous tissues were obtained from 130 patients. The D-loop of mtDNA sequence in noncancerous tissues was compared with that of pair...

A great deal of evidence is now available indicating that mutations play a dominant role in the aging process. Because carcinogenesis is one facet of the aging process, mu tations must play a major role here also. However, carcinogenesis certainly does not consist of the simple induction of a mutation in one cell which confers the property of uncontrolled growth on that cell and its progeny. Th...

Purpose: Hallmarks of germline BRCA1/2-associated ovarian carcinomas include chemosensitivity and improved survival. The therapeutic impact of somatic BRCA1/2 mutations and mutations in other homologous recombination DNA repair genes is uncertain. Experimental Design: Using targeted capture and massively parallel genomic sequencing, we assessed 390ovarian carcinomas for germline and somatic los...

Due to the high mutational somatic burden of Cutaneous Malignant Melanoma (CMM) a thorough profiling of the driver mutations and their interplay is necessary to explain the timing of tumorigenesis or for the identification of actionable genetic events. The aim of this study was to establish the mutation rate of some of the key drivers in melanoma tumorigenesis combining molecular analyses and/o...

At present there is much discussion on the relation of carcinogenesis to mutation. There are several puzzling problems to be considered, differing somewhat between cancers of spontaneous origin and those induced by some sort of treatment. The hereditary influence in the origin of spontaneous neoplasms has been repeatedly demonstrated, though there are many cases lacking such evidence. Here is a...

Mediterranean-type ecosystems are among the most remarkable plant biodiversity "hot spots" on the earth, and fire has traditionally been invoked as one of the evolutionary forces explaining this exceptional diversity. In these ecosystems, adult plants of some species are able to survive after fire (resprouters), whereas in other species fire kills the adults and populations are only maintained ...

The antigen binding specificity of an antibody molecule is determined by the amino acid sequences of the variable (V) 1 regions of the heavy (H) and light (L) chains. The antibody repertoire of an individual is large and complex. The studies of antibody polypeptides and genes in mice have suggested three sources of diversity: multiple germline V genes (1-4), rearrangement of three sets of H cha...