title: Mitochondrial DNA copy number in colorectal cancer: between tissue comparisons, clinicopathological characteristics and survival.
abstract: Low mitochondrial DNA (mtDNA) copy number in tumors has been associated with worse prognosis in colorectal cancer (CRC). This study further deciphers the role of mtDNA copy number in CRC by comparing mtDNA copy number between healthy, adenoma and carcinoma tissue, by investigating its association according to several clinicopathological characteristics in CRC, and by relating it to CRC-specific survival in CRC patients. A hospital-based series of samples including cancer, adenoma and adjacent histologically normal tissue from primary CRC patients (n = 56) and recurrent CRC (n = 16) was studied as well as colon mucosa samples from healthy subjects (n = 76). Furthermore, mtDNA copy number was assessed in carcinomas of 693 CRC cases identified from the population-based Netherlands Cohort Study (NLCS). MtDNA copy number was significantly lower in carcinoma tissue (P = 0.011) and adjacent tissue (P < 0.001) compared to earlier resected adenoma tissue and in primary CRC tissue compared to recurrent CRC tissue (P = 0.011). Within both study populations, mtDNA copy number was significantly lower in mutated BRAF (P = 0.027 and P = 0.006) and in microsatellite unstable (MSI) tumors (P = 0.033 and P < 0.001) and higher in KRAS mutated tumors (P = 0.004). Furthermore, the association between mtDNA and survival seemed to follow an inverse U-shape with the highest HR observed in the second quintile of mtDNA copy number (HR = 1.70, 95% CI = 1.18, 2.44) compared to the first quintile. These results might reflect an association of mtDNA copy number with various malignant processes in cancer cells and warrants further research on tumor energy metabolism in CRC prognosis.
authors.forename: Frits H M
authors.initials: FH
authors.lastname: van Osch
authors.affiliation: Department of Clinical Genetics and.
authors.forename: An M
authors.initials: AM
authors.lastname: Voets
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Schouten
authors.affiliation: Department of Clinical Genetics and.
authors.forename: Ralph W H
authors.initials: RW
authors.lastname: Gottschalk
authors.forename: Colinda C J M
authors.initials: CC
authors.lastname: Simons
authors.affiliation: Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht 6200MD, The Netherlands.
authors.forename: Manon
authors.initials: M
authors.lastname: van Engeland
authors.affiliation: Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht 6200MD, The Netherlands.
authors.forename: Marjolein H F M
authors.initials: MH
authors.lastname: Lentjes
authors.forename: Piet A
authors.initials: PA
authors.lastname: van den Brandt
authors.affiliation: Department of Clinical Genetics and.
authors.forename: Hubert J M
authors.initials: HJ
authors.lastname: Smeets
authors.forename: Matty P
authors.initials: MP
authors.lastname: Weijenberg
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000401:mortality; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies
chemical_list: D004272:DNA, Mitochondrial