Highlights d Molecular subtypes and genetics shape immune landscape in hematological malignancies d Cytotoxic T/NK cell infiltration in MDS-like AML with TP53 mutations and ABC DLBCL d Methylation changes suppress HLA genes in AML and induce cancer antigens in myeloma d Cancer type-specific targets such as VISTA in myeloid and CD70 in lymphoid cancers

We report the immunogenomic landscape of >10,000 hematological malignancies by integrating large-scale genomic, epigenomic, and transcriptomic datasets in this article. During its preparation, we submitted an incorrect version of Figure 1A, in which the numbers of the cases in the Hemap dataset were incorrect (1,288 and 4,293 lymphoma and leukemia samples, respectively; the correct numbers are 1,300 and 4,281). Similarly, in Figure S1A, the number of cell lines in CCLE dataset was incorrect (CHL n = 9 changed to n = 8, and unknown n = 7 is now included). The number of cases reported in the first paragraph of the Results section has also been corrected to reflect these revisions (''We used 7,092 samples from 36 hematological malignancies, with 770 healthy donor hematological cell populations and 610 cell lines as controls [Pö lö nen et al., 2019], to comprehensively analyze immunological properties in hematological cancer transcriptomes [Figures 1A and S1A; Table S1]''). These errors do not affect any of the data or conclusions in the article, and the figures have been revised in the online and printed versions of the paper, which differ from the version originally published online on July 9, 2020. We apologize for any confusion these errors may have caused.

Lung cancers exhibit pronounced functional heterogeneity, confounding precision medicine. We studied how the cell of origin contributes to phenotypic heterogeneity following conditional expression of Kras and loss of Lkb1 (Kras;Lkb1). Using progenitor cell-type-restricted adenoviral Cre to target cells expressing surfactant protein C (SPC) or club cell antigen 10 (CC10), we show that Ad5-CC10-Cre-infected mice exhibit a shorter latency compared with Ad5-SPC-Cre cohorts. We further demonstrate that CC10 cells are the predominant progenitors of adenosquamous carcinoma (ASC) tumors and give rise to a wider spectrum of histotypes that includes mucinous and acinar adenocarcinomas. Transcriptome analysis shows ASC histotype-specific upregulation of pro-inflammatory and immunomodulatory genes. This is accompanied by an ASC-specific immunosuppressive environment, consisting of downregulated MHC genes, recruitment of CD11b Gr-1 tumor-associated neutrophils (TANs), and decreased T cell numbers. We conclude that progenitor cell-specific etiology influences the Kras;Lkb1-driven tumor histopathology spectrum and histotype-specific immune microenvironment.

We report an autosomal recessive lethal syndrome characterized by multiple fetal malformations, the most obvious anomalies being the defective face and seemingly absent limbs, which are bound to the trunk and encased under the skin. We identified the molecular defect that causes this syndrome, using a combined strategy of gene-expression arrays, candidate-gene analysis, clinical studies, and genealogic investigations. A point mutation in two affected fetuses led to the loss of the conserved helix–loop–helix ubiquitous kinase (CHUK), also known as IκB kinase α. CHUK has an essential role in the development of skin epidermis and its derivatives, along with various other morphogenetic events. (Funded by the Academy of Finland and others.).