The pan-cancer analysis of whole genomes The expansion of whole-genome sequencing studies from individual ICGC and TCGA working groups presented the opportunity to undertake a meta-analysis of genomic features across tumour types. To achieve this, the PCAWG Consortium was established. A Technical Working Group implemented the informatics analyses by aggregating the raw sequencing data from different working groups that studied individual tumour types, aligning the sequences to the human genome and delivering a set of high-quality somatic mutation calls for downstream analysis (Extended Data Fig. 1). Given the recent meta-analysis

T h e P a t h o l o g y o f F a m i l i a l B r e a s t C a n c e r : P r e d i c t i v e V a l u e o f I m m u n o h i s t o c h e m i c a l M a r k e r s E s t r o g e n R e c e p t o r , P r o g e s t e r o n e R e c e p t o r , H E R -2 , a n d p 5 3 i n P a t i e n t s W i t h M u t a t i o n s i n B R C A 1 a n d B R C A 2By Sunil R. Lakhani, Marc J. van de Vijver, Jocelyne Jacquemier, Thomas J. Anderson, Peter P. Osin, Lesley McGuffog, and Douglas F. Easton for the Breast Cancer Linkage ConsortiumPurpose: The morphologic and molecular phenotype of breast cancers may help identify patients who are likely to carry germline mutations in BRCA1 and BRCA2. This study evaluates the immunohistochemical profiles of tumors arising in patients with mutations in these genes.Materials and Methods: Samples of breast cancers obtained from the International Breast Cancer Linkage Consortium were characterized morphologically and immunohistochemically using antibodies to estrogen receptor, progesterone receptor, HER-2 (c-erbB-2 oncogene), and p53 protein.Results: Breast cancers in patients with BRCA1 germline mutations are more often negative for estrogen receptor, progesterone receptor, and HER-2, and are more likely to be positive for p53 protein compared with controls. In contrast, BRCA2 tumors do not show a significant difference in the expression of any of these proteins compared with controls.Conclusion: BRCA1 has a distinctive morphology and immunohistochemical phenotype. The combined morphologic and immunohistochemical data can be used to predict the risk of a young patient harboring a germline mutation in BRCA1. The BRCA2 phenotype is currently not well defined.