Somatic Mitochondrial DNA Point Mutations Used as Biomarkers to Demonstrate Genomic Heterogeneity in Primary Prostate Cancer

Table 1

Prognostic grade groups (ISUP 1–5), consecutive prostate specimen, and the related sample number.

ISUP grade	Prostate #	Sample	Distance between samples (mm)	Mutant fraction (MF) in positive fragments			Mutation found by LCM when MF was 0% in initial analysis
1	1	1	8	11.3%	20%
		2		13.6%	9.3%
1	2	3	26
		4
1	3	5	16	9.6%	0%			Yes
		6		0%	12.6%		Yes
1	4	7	21	20.1%	0%			Yes
		8		16.1%	36.1%
3	5	9	7	37.9%
		10		13.5%
3	6	11	9	12.7%	42.8%	2.2%
		12		0%	0%	0%	Yes	Yes	Yes
3	7	13	10
		14
3	8	15	7	31%	36.9%	53.3%	Yes	Yes
		16		0%	0%	30.8%	Yes
5	9	17	4	0%
		18		20%
5	10	19	9
		20
5	11	21	3	6%	30%
		22		4.8%	0%			Yes
5	12	23	13	10%
		24		40%

Each specimen is represented by two samples. The sample number is used as a reference in all figures. The distance between the two collected samples from each index tumor was recorded with an average intratumoral distance of 11.1 mm (±6.8 mm). The samples from prostate 2 and 4 were collected from different tumor foci. Initial sample scan analysis was registered pairwise and 9/12 had one or more fragments with a detectable mutant fraction. This mutant fraction is reported as percentage. To increase the limit of detection, all nine sample pairs were subjected to LCM and CTCE analysis. All mutations detected in the initial scan were verified by this procedure. In the initial scan, tumor numbers 2, 7, and 10 did not demonstrate any positive mutant fractions in any fragments.