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• Hematology (JJ Schuringa)

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• What is the definition of oncogenes and proto-oncogenes?

  An oncogene is a mutated gene that contributes to the development of a cancer. In their normal, unmutated state, oncogenes are called proto-oncogenes, and they play roles in the regulation of cell division.

• What is the definition of a tumor suppressor gene? How can the mutation of a tumor suppressor gene contribute to the development of cancer?

  Genes in the body that can suppress or block the development of cancer.
  
  A tumor suppressor gene directs the production of a protein that is part of the system that regulates cell division. The tumor suppressor protein plays a role in keeping cell division in check. When mutated, a tumor suppressor gene is unable to do its job, and as a result uncontrolled cell growth may occur. This may contribute to the development of a cancer.

• What are copy number alterations (CNAs)? And in what does this presumably result in human cancer?

  Copy number alterations (CNAs) are somatic changes to chromosome structure that result in gain or loss in copies of sections of DNA, and are prevalent in many types of cancer.
  
  Copy-number alterations are very frequent in human cancers, presumably resulting in enhanced expression of growth-promoting genes.

• What is the normal function of the H-RAS gene? Which protein does it produce and what is its function?

  The HRAS gene provides instructions for making a protein called H-Ras that is involved primarily in regulating cell division.Through a process known as signal transduction, the H-Ras protein relays signals from outside the cell to the cell's nucleus.

• What mutation in the H-RAS gene has been associated with bladder cancer?

  Gly12Val mutation that can cause epidermal nevi

• What does the Gly12Val mutation in the HRAS gene lead to?

  As a result of this genetic change, the altered H-Ras protein becomes continuously active within the cell.
  The overactive H-Ras protein directs the cell to grow and divide abnormally, leading to uncontrolled cell division and the formation of a tumor. 

• What are (active) promotors?

  In genetics, a promoter is a region of DNA that leads to initiation of transcription of a particular gene. Promoters are located near the transcription start sites of genes, upstream on the DNA (towards the 5' region of the sense strand).

• What is gene amplification?

  Gene amplification is a copy number increase of a restricted region of a chromosome arm. It is prevalent in some tumors and is associated with overexpression of the amplified gene(s). Amplified DNA can be organized as extrachromosomal elements, as repeated units at a single locus or scattered throughout the genome.

• In what three ways can chromosomal translocations result in enhanced expression of oncogenes?

  - fusion to active promotors (MYC)
  - loss of negative regulation via microRNAs (let7 - HMGA2)
  - fusion proteins with altered function (BCR - ABL)

• There is a continuous process of cell division and cell death, how many new cells per day?

  1 billion