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Updated: Jun 27, 2026
Capturing Common Fragile Site Breaks by Native γH2A.X ChIP
Published on: January 24, 2025
Loss expression of active fragile sites genes associated with the severity of breast epithelial abnormalities
Tian-tian Wang1, Eldo E Frezza, Rong Ma
1Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
Background:
WWOX and FHIT are two candidate tumor suppressor genes located in active fragile sites, the damage of which has been associated with the development of breast cancer. The association of the expression of these genes and the development of breast cancer has not been fully explored. We evaluated mRNA and protein expression of WWOX and FHIT in breast tissue with normal histological appearances, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive cancer to see if a progressive decline in expression was present.
Methods:
Reverse transcription-polymerase chain reaction and Western blotting were used to evaluate the specimens for mRNA and protein expression, including 28 specimens with normal tissue, 28 specimens with atypical ductal hyperplasia, 33 specimens with ductal carcinoma in situ, and 51 specimens with invasive ductal carcinoma.
Results:
Compared with in situ and invasive cancer specimens, both normal and atypical hyperplasia specimens had greater rates of detectable mRNA (WWOX rate ratio = 2.95, 95% CI 1.24 - 7.08; FHIT rate ratio = 4.58, 95% CI 1.82 - 11.81) and Western blotting detectable protein (WWOX rate ratio = 4.12, 95% CI 1.63 - 10.73; FHIT rate ratio = 3.76, 95% CI 1.44 - 10.06). For both proteins, differences between normal and atypical hyperplasia specimens and between in situ and invasive carcinoma specimens were explainable by chance (P > 0.05 for each analysis). Within each histological category, differences among fractions of specimens showed that FHIT and WWOX mRNA and protein expression were explainable by chance (P > 0.05 for each analysis).
Conclusion:
Expression of FHIT and WWOX decreases along with breast tissue progress from a normal histological appearance to atypical ductal hyperplasia, in situ cancer, and the final invasive cancer.
Insights
Tumor suppressor genes, WWOX and FHIT, show decreased expression in breast cancer progression. This decline is observed from normal tissue to invasive cancer, indicating their potential role in breast cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- WWOX (WW domain-containing oxidoreductase) and FHIT (Fragile histidine triad) are tumor suppressor genes located at fragile sites implicated in breast cancer.
- The precise association between WWOX and FHIT gene expression and breast cancer development requires further investigation.
Purpose of the Study:
- To evaluate the mRNA and protein expression levels of WWOX and FHIT in breast tissues.
- To determine if a progressive decline in WWOX and FHIT expression correlates with the progression of breast tissue from normal to cancerous states.
Main Methods:
- Utilized reverse transcription-polymerase chain reaction (RT-PCR) for mRNA expression analysis.
- Employed Western blotting for protein expression analysis.
- Examined 28 normal tissues, 28 atypical ductal hyperplasia, 33 ductal carcinoma in situ, and 51 invasive ductal carcinoma specimens.
Main Results:
- Normal and atypical hyperplasia tissues exhibited significantly higher rates of detectable WWOX and FHIT mRNA and protein compared to in situ and invasive cancer tissues.
- No statistically significant differences in WWOX and FHIT expression were found between normal and atypical hyperplasia, nor between in situ and invasive carcinoma.
- Expression levels within each histological category were not significantly different, suggesting a general trend of decline across stages.
Conclusions:
- WWOX and FHIT expression diminishes as breast tissue progresses from normal histology through atypical hyperplasia and carcinoma in situ to invasive cancer.
- The findings suggest a role for WWOX and FHIT in breast cancer development, with reduced expression correlating with disease progression.
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