Microsatellite Alterations With Allelic Loss at 9p24.2 Signify Less-Aggressive Colorectal Cancer Metastasis
- Minoru Koi 1, Melissa Garcia 2, Chan Choi 3, Hyeong-Rok Kim 4, Junichi Koike 5, Hiromichi Hemmi 6, Takeshi Nagasaka 7, Yoshinaga Okugawa 8, Yuji Toiyama 9, Takahito Kitajima 9, Hiroki Imaoka 9, Masato Kusunoki 9, Yin-Hsiu Chen 10, Bhramar Mukherjee 10, C Richard Boland 2, John M Carethers 11
- Minoru Koi 1, Melissa Garcia 2, Chan Choi 3
- 1Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Gastrointestinal Cancer Research Laboratory, Baylor Research Institute and Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas.
- 2Gastrointestinal Cancer Research Laboratory, Baylor Research Institute and Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas.
- 3Department of Pathology, Chonnam National University Medical School, Gwangju, Korea.
- 4Department of Surgery, Chonnam National University Medical School, Gwangju, Korea.
- 5Department of Surgery, Toho University Faculty of Medicine, Tokyo, Japan.
- 6Department of Molecular Immunology, Toho University Faculty of Medicine, Tokyo, Japan.
- 7Department of Gastroenterological Surgery and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
- 8Gastrointestinal Cancer Research Laboratory, Baylor Research Institute and Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas; Department of Gastrointestinal and Pediatric Surgery, Graduate School of Medicine Mie University, Mie, Japan.
- 9Department of Gastrointestinal and Pediatric Surgery, Graduate School of Medicine Mie University, Mie, Japan.
- 10Department of Biostatistics School of Public Health, University of Michigan, Ann Arbor, Michigan.
- 11Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
- 0Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Gastrointestinal Cancer Research Laboratory, Baylor Research Institute and Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas.
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View abstract on PubMed
Summary
This summary is machine-generated.Elevated microsatellite alterations (E/L) and 9p24.2 loss of heterozygosity (LOH) in colorectal cancer may predict less aggressive metastasis. This finding offers a potential biomarker for improved patient outcomes in stage III colorectal cancer.
Area Of Science
- Oncology
- Cancer Genetics
- Molecular Biology
Background
- Colorectal cancer (CRC) recurrence and metastasis mechanisms post-treatment are unclear.
- Elevated microsatellite alterations at selected tetranucleotide repeats and low levels of microsatellite instability (E/L) are linked to higher recurrence risk in stage II/III CRC.
- Hypoxia/inflammation may induce E/L by reducing nuclear MSH3, promoting metastasis.
Purpose Of The Study
- Identify genetic alterations in primary colorectal tumors associated with liver metastasis.
- Determine the impact of these alterations on patient survival.
- Investigate the relationship between E/L, MSH3 deficiency, and metastatic patterns.
Main Methods
- Analyzed primary colorectal tumors and matched liver metastases from 156 stage II/III patients.
- Examined 141 microsatellite loci for frame-shift mutations and loss of heterozygosity (LOH) indicative of MSH3 deficiency.
- Assessed the association of highly altered loci with E/L and correlated findings with patient outcomes.
Main Results
- Loss of heterozygosity at chromosome 9p24.2 (9p24.2-LOH) was significantly associated with E/L in liver metastases (OR=10.5, P=.0007).
- No significant differences in E/L or 9p24.2-LOH were observed between primary tumors and metastases.
- Patients with E/L and 9p24.2-LOH showed increased survival post-recurrence (HR=0.25, P=.0001) and E/L with 9p24.2-LOH was an independent prognostic factor for overall survival in stage III CRC (HR=0.06, P=.01).
Conclusions
- The combination of E/L and 9p24.2-LOH may serve as a biomarker.
- This biomarker appears to indicate less aggressive metastasis in stage III primary colorectal tumors.
- Further research can explore therapeutic strategies targeting these molecular pathways.
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