Table 1.

mtDNA changes in pancreatic cancer and clinical significance.

mtDNA Region Analyzed	Analysis	Samples	Findings and Clinical Correlations	References
Whole mtDNA	mtDNA content	43 resectable PDACs and 31 adjacent normal pancreatic tissues	mtDNA depletion detected in pancreatic cancer. mtDNA content inversely correlated with tumor grade. No correlation with patient survival.	[36]
D-loop	Mutations	99 cases of pancreatic cancer, 42 cases of chronic pancreatitis, 18 cases of tumors of the pancreatobiliary tract, and 87 healthy controls	3/99 pancreatic cancer patients displayed mutations. T16519C SNP correlated with diabetes mellitus and worse prognosis.	[38]
D-loop 12S rRNA 16S rRNA ND2 ND3 ND4 ND5 COI COII CYTB ATPase6 tRNA	24 SNPs, including T16519C	955 primary pancreatic adenocarcinomas from Caucasian patients and 1102 healthy Caucasian controls; 990 pancreatic cancer patients	No association of the 24 SNPs with pancreatic cancer risk or survival.	[40,41]
Whole mtDNA	Mutations	286 pancreatic cancer cases and 283 controls	ND2 mt5460g (complex I), COIII mt9698c (complex IV), mt1811g (16S), mt12307g (tRNA), and mt150t (HV2) associated with pancreatic cancer; 19 haplogroup N/L-specific variants showed a statistically significant association with pancreatic cancer.	[42]
Whole mtDNA + ~1000 nuclear genes encoding mitochondrial proteins and metabolic enzymes	Mutations	12 patient-derived pancreatic cancer cell lines	24 mtDNA somatic mutations and 18 nuclear DNA mutations were identified. Mutations were phenotypically associated with mitochondrial dysfunction.	[43]
Whole-genome sequencing	Mutations	268 early-stage resected PDACs and paired nontumor tissues;for 6 patients, primary tumor and metastasesanalyzed	304 mtDNA somatic mutations, with at least 1 mutation in 61% of the patients.60/304 mutations in the noncoding region. Metastases have a higher number of mtDNA mutations and thus may represent an adverse prognostic marker.	[45]