Role of FHIT in human cancer

C M Croce1, G Sozzi, K Huebner

  • 1The Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19107-5799, USA.

Insights

The FHIT gene, located at chromosome 3p14.2, is inactivated in epithelial cancers, especially those linked to environmental carcinogens. Its expression levels may offer crucial diagnostic and prognostic insights for cancer patients.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • The FHIT (Fragile Histidine Triad) gene is located at chromosome 3p14.2, a region frequently altered in various human cancers.
  • Tumorigenesis involves genetic alterations, including gene inactivation, particularly in epithelial malignancies.

Purpose of the Study:

  • To clone and characterize the FHIT gene and investigate its role in cancer development.
  • To determine the significance of FHIT gene alterations in epithelial tumors, especially those related to environmental exposures.
  • To evaluate the potential of FHIT expression as a diagnostic and prognostic marker in premalignant and malignant tissues.

Main Methods:

  • Analysis of hemizygous and homozygous deletions in human cancer tissues.
  • Cloning and characterization of the FHIT gene.
  • Immunohistochemical detection of Fhit protein expression in premalignant and malignant tissues.

Main Results:

  • The FHIT gene was identified and characterized at chromosome region 3p14.2.
  • FHIT is inactivated in epithelial tumors, with alterations occurring early in cancers linked to environmental carcinogens.
  • In some cancers, Fhit inactivation appears to be a later event, potentially correlating with tumor progression and aggressiveness.

Conclusions:

  • FHIT gene inactivation is implicated in the development of various epithelial cancers.
  • The timing of FHIT inactivation may differ depending on the cancer type and its association with environmental factors.
  • Assessing Fhit expression via immunohistochemistry could yield valuable diagnostic and prognostic information for cancer management.

Related Concept Videos

FISH - Fluorescent In-situ Hybridization02:07

FISH - Fluorescent In-situ Hybridization

Fluorescence in situ hybridization, or FISH, was developed in the early 1980s and has quickly become one of the most widely used techniques in cytogenetics. Labeled probes are used to bind complementary DNA or RNA sequences on a chromosome or in a region within a cell. Earlier, the probes could only be obtained by cloning or reverse transcription of a DNA template. Currently, the probe oligonucleotides can be synthesized synthetically. Additionally, with the advancement of optical techniques,...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...