Fig. 6: Recurrent complex PVs in additional families.

Visual representation of the partial duplication of MSH2 exon 15, contributing to the SV in the BAM file observed in patient #A as well as patient #97 (A). Note: Read depths of patient #97 and control are also demonstrated in Fig. 4A and are presented here for optimal comparison. Immunohistochemical analysis of the mismatch repair proteins in the prostate cancer biopsy of patient #A (B). 20× magnification. Pedigree of patient #A (C). Representative image of reads revealing the co-occurrence of MSH2 c.2042 A > C and c.2045 C > T on the same allele from the BAM file in patient #B (D). Yellow boxes represent the alternative C at the 2042 position, while blue boxes represent the alternative T at the 2045 position. Immunohistochemical analysis of the mismatch repair proteins in the pancreatic cancer specimen of patient #B (E). 20× magnification. Pedigree of patient #B (F). Electrophoretic separation of MLH1 c.[2078_2172del; 2080_*+493dup]-specific PCR (further elaborated in Fig. 2F–H) products on 1.5% agarose gel (G) performed on germline DNA sample of patients #C and #C2 and two independent controls. Note: patients #C and #C2 are highlighted also on Panel J. Note: Uncropped image is demonstrated in Figure S8. Chromatogram visualizing the breakpoint (vertical brown line) included in the breakpoint-specific PCR (H). MLPA analyses with default (P003-D1) and confirmation (P248-B2) probe sets (I). Pedigree of patient #C (J). bp base pair, CRC colorectal cancer, EC endometrial cancer, GC gastric cancer, KC kidney cancer, L DNA ladder, OC ovarian cancer, PanC pancreatic cancer, PC prostate cancer.