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Alterations in the mitochondrial displacement loop in lung cancers
Makoto Suzuki1, Shinichi Toyooka, Kuniharu Miyajima
1Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas Texas 75390, USA.
Summary
Mitochondrial DNA D-loop alterations, including changes in the polycytosine tract (PCT), are common in lung cancer cell lines and tumors. These alterations, particularly PCT changes, were more frequent in squamous cell carcinomas and larger tumors.
Area of Science:
- Genetics
- Oncology
- Mitochondrial DNA
Background:
- Alterations in the mitochondrial DNA (mtDNA) D-loop are frequently observed in various cancers.
- These alterations include changes in the polycytosine tract (PCT) and single base substitutions (SBS).
Purpose of the Study:
- To investigate the frequency of D-loop alterations in lung cancer cell lines and tumors.
- To correlate these alterations with clinicopathologic features of lung cancer.
Main Methods:
- Sequencing of the entire D-loop in 28 lung cancer cell lines (SCLC and NSCLC) and matched B-lymphoblastoid cell lines.
- Determination of the polycytosine tract (PCT) length in 55 resected NSCLC tumors and corresponding nonmalignant lung tissues.
Main Results:
- D-loop alterations were found in 61% of lung cancer cell lines, including SBS (29%) and PCT changes (50%).
- PCT changes were present in 20% of NSCLC tumors and were associated with higher frequency in squamous cell carcinomas (32%) and larger tumors (35%).
- PCT changes in tumors were absent when the nonmalignant tissue had a PCT repeat number of seven.
Conclusions:
- D-loop alterations are frequent in lung cancer cell lines and tumors.
- PCT alterations show a weak association with specific clinical parameters like tumor histology and size.
- Tumor PCT changes are linked to variations from the common PCT repeat number in adjacent nonmalignant lung tissue.