Whole Genome Sequencing Will Cost £1000 Per Patient By 2015. How Will This Change Cancer Medicine?

2556 words - 10 pages

Whole genome sequencing will cost £1000 per patient by 2015. How will this change cancer medicine?IntroductionCancer is a general term for a large group of diseases characterized by unregulated cell division and growth. These cells form malignant tumours whose constituent parts can migrate and invade elsewhere in the body. Its notoriety is warranted due to its high prevalence, mortality and insidious onset. Treatment is currently suboptimal - about half of all invasive cancers cause death in the patient [1]. Chemotherapy, radiotherapy and surgery all aim at decreasing tumour size, but are often not curative. As whole genome sequencing becomes cheaper, it is feasible that it will become incorporated into routine investigations for new cancer patients, providing valuable insight into each specific tumour.Genetic BackgroundCancer is currently classified by tissue of origin (carcinomas, sarcomas, adenocarcinomas) and organ of origin [2]. There are over 200 different types of cancer, with different mechanisms of pathology, making it an extremely heterogeneous disease. Despite this, it is possible to hallmark every cancer with six features [3]:Growth signal autonomyEvasion of growth inhibitory signalsEvasion of apoptosisUnlimited replicative potentialAngiogenesisInvasion and metastasisThese features come to fruition via genetic mutation and subsequent transcription - cancer is as a result of unrectified alterations to DNA via UV/ionising radiation, chemical carcinogens, infectious pathogens, and endogenous regulatory failure [2]. It is therefore a genetic disease potentially occurring both somatically and in germ line cells.There are two groups of genes that are specifically mutated in malignancy: tumour suppressor genes and oncogenes [4]. The physiological role of tumour suppressor genes is to arrest inappropriate cell growth and repair DNA. A loss-of-function mutation is recessive and so must occur in both copies of the gene. This is known as the two-hit hypothesis, described by Knudson in 1978[5], a long time prior to the human genome project. In the time since there have been many (15+) specific tumour suppressor genes identified whose mutation is associated with inherited cancers, for example APC and colorectal cancers. However, mutations more commonly are spontaneous, highlighted by the fact that only 5%-10% of all cancers are inherited [6].Oncogenes are activated by chromosomal rearrangement, mutation and amplification [7], and the products released correspond to the six hallmarks of malignancy: transcription factors, chromatin remodelers, growth factors, growth factor receptors, signal transducers, and apoptosis regulators. They are autosomally dominant somatic mutations; one mutation will cause a direct change in the daughter cells.Conventional TreatmentsCytotoxic chemotherapy is a front-line method for tumour reduction. The principle is to cause catastrophic damage in rapidly dividing cells; tumour cells, haematocytes, stomach, and hair...

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