Fig. 6.

Integrated analyses of the associations between mitochondrial mutations and mitochondrial gene expression profiles. A CNV pattern and sampling strategy of patient #6. Adenomas have no obvious CNVs and different subclones with distinct CNV patterns are found in primary tumors. Lymph node metastasis has different CNV patterns with primary tumors. A: adenoma. PT: primary tumors. LyM: lymph node metastasis; LyM1, LyM2, and LyM3 represent three separated lymph node metastatic tumors. The pie charts reflect the proportion of different subclones in each region. Copy number gain and copy number loss were indicated with red and blue respectively. Different tissues were divided by bold black solid lines, and different clones within the same tissue block were divided by black dashed lines. The squares above the heatmap represent different chromosomes, black squares represent odd-numbered chromosomes and chromosome X, and light gray squares represent even-numbered chromosomes and chromosome Y. The squares on the left of the heatmap represent different subclones, and the same color represents the same clone. The most obvious copy number differences between different clones were highlighted by different colored boxes. B Heatmap showing selected mitochondrial mutations of patient #6. Blue, orange, red, and gray represent wild-type, heterozygous, and homozygous mutations and undefined (read depth < 9X) respectively. The triangle, circle and star represent the mutation state at the position 1,670-, 927-, and 8277-point site of mitochondria. C The diagram showing the tumor metastasis path of patient #6. The triangle, circle, and star represent the mutation state at the position 1,670-, 927-, and 8277-point site of mitochondria. Their colors represent the mutation status: blue, orange, red, and gray represent wild-type, heterozygous, and homozygous mutations respectively. D The boxplot showing the relative expression levels of MT-TV for patient #6 and patient #1. Other patients without MT-TV mutations have a similar pattern as patient #1 (data not shown). N: adjacent normal tissue. A: adenoma. PT: primary tumor. LyM: lymph node metastasis and LyM1-LyM3 represent three separated lymph node metastatic tumors. E The mutation state of mitochondrial gene MT-TV (site: 1,670) that is defined by whole exome sequencing data. Gray rectangle represents the wild-type, and the red rectangle represents the mutant type. The bar plot shows the allele frequency of mutations at this site. N: adjacent normal tissue. A: adenoma. PT: primary tumor. LyM: lymph node metastasis. LM: liver metastasis. For patients #10–#12, cells in the adjacent normal tissues were enriched by MACs or FACs; N represents EPCAM-positive cells and N_Neg represents EPCAM-negative cells. 1 cm, 3 cm, 10 cm, and 20 cm represent the distance to the edges of the tumor