Microbiology and Immunology

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O157:H7 INFECTION•seeE. COLIO157:H7

INFECTION

OOncogeneNCOGENE

An oncogene is a special type of genethat is capable of trans-

forming host cells and triggering carcinogenesis. The name is

derived from the Greek onkos, meaning bulk, or mass, because

of the ability to cause tumor growth. Oncogenes were first dis-

covered in retroviruses (viruses containing the enzyme

reverse transcriptase, and RNA, rather than DNA) that were

found to cause cancer in many animals (e.g., feline leukemia

virus, simian sarcoma virus). Although this is a relatively

common mechanism of oncogenesis in animals, very few

oncogene-carrying viruses have been identified in man. The

ones that are known include the papilloma virus HPV16 that

is associated with cervical cancer, HTLV-1 and HTLV-2 asso-

ciated with T-cell leukemia, and HIV-1 associated with Kaposi

sarcoma.

Studies of humans led to the discovery of related genes

called proto-oncogenes that exist naturally in the human

genome. These genes have DNA sequences that are similar to

oncogenes, but under normal conditions, the proto-oncogenes

do not cause cancer. However, specific mutationsin these

genes can transform them to an oncogenic form that may lead

to carcinogenesis. So, in humans, there are two unique ways in

which oncogenesis occurs, by true viral infection and by muta-

tion of proto-oncogenes that already exist in human cells.

See also Molecular biology and molecular genetics;

Oncogenetic research; Viral genetics; Viral vectors in gene

therapy; Virology; Virus replication; Viruses and responses to

viral infection

OOncogene researchNCOGENE RESEARCH

Research into the structure and function of oncogenes has

been a major endeavor for many years. The first chromosome

rearrangement (Ph’) involving a proto-oncogene to be

directly associated with cancer induction was identified in

1960. Since then, over 50 proto-oncogenes have been mapped
      in the human genome, and many cancer-related mutations
      have been detected. Once the role of oncogenes and proto-
      oncogenes in cancer was understood, the task of elucidating
      the exact mutations, specific breakpoints for translocations,
      and how protein products are altered in the disease process
      was undertaken.
      Karyotype analysis has been used for many years to
      identify chromosome abnormalities that are specifically asso-
      ciated with particular types of leukemia and lymphoma aiding
      in diagnosis and the understanding of prognosis. Now that
      many of the genes involved in the chromosome rearrange-
      ments have been cloned, newer, more effective detection
      techniques, have been discovered. FISH, fluorescence in situ
      hybridization, uses molecular probes to detect chromosome
      rearrangements. Probes are developed to detect deletions or
      to flank the breakpoints of a translocation. or example, using
      a dual color system for chronic myelogenous leukemia
      (CML), a green probe hybridizes just distal to the c-abllocus
      on chromosome 9 and a red probe hybridizes just proximal to
      the locus on chromosome 22. In the absence of a rearrange-
      ment, independent colored signals (two green and two red)
      are observed. When the rearrangement occurs, two of the flu-
      orescent probes are moved adjacent to one another on one
      chromosome and their signals merge producing a new color
      (yellow) that can be easily detected (net result: one green, one
      red, and one yellow signal).
      Other molecular techniques such as Southern blotting
      and PCRare also used for cancer detection and can identify
      point mutations as well as translocations. These systems are
      set up such that one series of DNAfragments indicate no muta-
      tion, and a different size fragment or series of fragments will

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