Fig. 3

HRD genomic features in breast cancers with and without bi-allelic PALB2 inactivation. a Mutational signatures of all somatic SNVs in the 16 PALB2-associated breast cancers sequenced by whole-exome sequencing (left) as inferred by deconstructSigs⁴¹ based on the 30 signatures represented in COSMIC, and a bar plot indicating the proportion of the major mutational signatures identified in each case (right), in decreasing proportion of each signature. The dominant mutational signatures were assigned according to Alexandrov et al.,⁴⁰ following the consensus of at least two of three approaches (deconstructSigs based on 30 signatures from COSMIC, based on the 12 signatures known to occur in breast cancer, and NMF method⁴² based on 30 signatures from COSMIC) where signature 1 relates to aging and signature 3 to defective homologous recombination DNA repair, and are shown for cases with bi-allelic PALB2 alterations (top) and mono-allelic PALB2 alterations (bottom). The number of SNVs is shown in parentheses. Sig signature, SNV single nucleotide variant. b Large-scale state transition (LST) scores of the four PALB2-associated breast cancers with mono-allelic PALB2 alterations and the 12 PALB2-associated breast cancers with bi-allelic PALB2 alterations. The median LST scores, and the 75th and 25th percentiles are displayed at the top and bottom of the boxes, respectively. Each dot corresponds to the LST score and the mutational signature of a given case. Dominant mutational signatures are color-coded according to the legend. Comparisons of LST scores between groups were performed using the Mann–Whitney U test. c Average deletion length (nucleotides) in PALB2-associated breast cancers with mono-allelic PALB2 alterations (n = 3) and with bi-allelic PALB2 alterations (n = 11). Only PALB2-associated breast cancers harboring small insertions and deletions were included in the analysis. The median value of deletion length, and the 75th and 25th percentiles are displayed at the top and bottom of the boxes, respectively. Comparisons of deletion lengths between groups were performed using the Mann–Whitney U test. d Number of genes affected by copy number alterations (CNAs) of the four PALB2-associated breast cancers with mono-allelic PALB2 alterations and the 12 PALB2-associated breast cancers with bi-allelic PALB2 alterations. The median value of the number of genes with CNAs, and the 75th and 25th percentiles are displayed at the top and bottom of the boxes, respectively. Comparisons were performed using Fisher’s exact test