case_images: PMC10890799_01
case_images: a Circos plot of breast cancer genome of case 1. From the outside of the circle to the inside, the following elements are arranged in their respective orders: cytoband, variant allele fraction of point mutations, intermutational distance of point mutations (logarithmic scale), copy number of each allele (red lines represent major, blue lines represent minor), total copy number (represented by black dots), and structural variations (represented by colored lines). b Somatic BRCA2-disrupting structural variation (inversion) between BRCA2 gene and DGKH gene and loss of heterozygosity in BRCA2 gene (minor copy number: 0).
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case_images: F1
case_images: Fig. 1), and suspicious lymph nodes were not seen, suggesting clinical T2N0M0. Cancer WGS, with 87% tumor cell fraction and an average ploidy of 2.1, identified 10,664 base substitutions, 3,422 indels, 411 structural variations somatically acquired, and genome-wide copy number alterations (Fig. 1a). Table S1-3) encompassed a BRCA2-disruptive inversion accompanied by a LOH (Fig. 1b).
case_images: PMC10890799_02
case_images: Circos plot of cancer genome and HRD score of case 2. a Right breast. b Left ovary.
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case_images: F2
case_images: Fig. 2a) and an enlarged lymph node suspected of metastasis in the right axillary level I, suggesting clinical T2N1. Fig. 2b) showed internal T2 high signal intensity with enhancing solid components, indicating primary ovarian cancers rather than metastases. The breast tumor tissue had a 48% tumor cell fraction, mean ploidy of 3.5, 7,493-point mutations, 268 structural variations, and diverse copy number changes (Fig. 2a), with LOH of BRCA1 and a positive HRD score (0.77). The ovarian tumor tissue exhibited a 40% fraction, mean ploidy of 4.0, 5,190-point mutations, 268 structural variations, and copy number changes (Fig. 2b).
case_images: PMC10890799_03
case_images: a Circos plot of breast cancer genome of case 3. b Sequencing and computational assessment of microsatellite instability (MSI) status by MSIsensor2. c Pentaplex PCR assessment of MSI status. d Immunohistochemical assessment of MSI status.
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case_images: F3
case_images: WGS results showed a 55% tumor cell fraction, mean ploidy of 1.6, 22,545 base substitutions, 75,150 indels, and 43 structural variations (Fig. 3). Fig. 3b). Fig. 3c), and disease progression was confirmed through subsequent surgery with a 3.8 cm tumor and five metastatic lymph nodes (5/12), suggesting ypT2N2a.
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case_images: Complex arrangement of germline TP53 in case 4.
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case_images: F4
case_images: The germline WGS showed a structurally disrupted TP53 due to complex rearrangements involving genomic insertion of a nuclear mitochondrial DNA segment (NUMT; Fig. 4).