Clinical characteristics of MDACC cohort.

<p>Clinical characteristics of MDACC cohort.</p

Validation of genomic markers of chemosensitivity in the TCGA triple negative breast cancer cohort.

<p>(A) Somatic and germline mutations in AR/FOXA1 pathway and CMB in the TCGA TNBC cohort. (B) Kaplan-Meier estimator of overall survival outcomes by AR/FOXA1 mutational status. Tumors carrying at least one mutation in the AR/FOXA1 pathway had significantly better overall survival compared to WT tumors (log-rank test, <i>p</i> = 0.028). (C) Overall survival outcomes of TCGA TNBC cases by CMB category. Cases with high CMB have significantly better overall survival (log-rank test, <i>p</i> = 0.025). AR, androgen receptor; CMB, clonal mutation burden; TCGA, The Cancer Genome Atlas; TNBC, triple negative breast cancer; WT, wild-type.</p

Genomic markers predictive of chemosensitivity in the MDACC triple negative breast cancer dataset.

<p>(A) Mutations in combined “regulation of androgen receptor activity” and “FOXA1 transcription factor network” pathways in the MDACC samples. (B) pCR rate by mutation status of the AR/FOXA1 pathway. The pCR rate was significantly higher (94.1%) in the cancers carrying at least one mutation in the AR/FOXA1 pathway compared to WT (16.6%) by the Fisher exact test (<i>p</i> < 0.001). (C) pCR rate by CMB category. CMB was defined based on MR and clonal heterogeneity. Tumors with high CMB appear to be extremely chemosensitive. AR, androgen receptor; CMB, clonal mutation burden; MDACC, MD Anderson Cancer Center; MR, mutation rate; Mut, mutation; pCR, pathologic complete response; RD, residual disease; WT, wild-type.</p

BRCA deficiency characterized by low wild-type transcript abundance defines a unique subtype of triple negative breast cancer.

<p>(A) Low WT BRCA1 abundance summarizes BRCA1 deficiency through multiple types of genomic aberrations. Arrow indicates the BRCA1 deficiency threshold. (B) Low WT BRCA2 abundance summarizes BRCA2 inactivation by multiple types of genomic aberrations. Arrow indicates BRCA2 deficiency threshold. (C) Number of silent or non-silent mutations, mutation signatures, and BRCA deficiency in TCGA TNBCs. BRCA-D, BRCA-deficient; BRCA-N, BRCA-normal; CNV, copy number variation; MMR, mismatch repair; Mut, mutation; SNV, single nucleotide variant; TCGA, The Cancer Genome Atlas; TNBC, triple negative breast cancer; WT, wild-type.</p

Clonal mutation burden and BRCA deficiency linked to immune activation in triple negative breast cancer.

<p>(A) Correlation between overall mutation rate and number of predicted neoantigens in TNBC. (B) Expression of immune metagenes as a function of the estimated clonality of tumors. Clonal tumors are associated with a significantly enhanced immune presence. (C) Estimated number of predicted neoantigens per clone in TNBC cases of different CMB categories. (D) Expression of immune metagenes in TNBC cases with different CMB. Both the number of neoantigens per clone and the immune presence are greater in tumors with high CMB. BRCA-D, BRCA-deficient; BRCA-N, BRCA-normal; CMB, clonal mutation burden; TCGA, The Cancer Genome Atlas; TNBC, triple negative breast cancer.</p

Diagram for selecting triple negative breast cancer samples from the TCGA breast cancer dataset.

<p>ACT, anthracycline/taxane; CNV, copy number variation; ER, estrogen receptor; Exomeseq; exome sequencing; IHC, immunohistochemistry; PR, progesterone receptor; RNAseq, RNA sequencing; TCGA, The Cancer Genome Atlas; TNBC, triple negative breast cancer.</p

Demographic, pregnancy, and birth history comparisons of nonsyndromic^a cases across major types of congenital heart defect in the Pediatric Cardiac Genetic Consortium Cohort.

<p>Demographic, pregnancy, and birth history comparisons of nonsyndromic<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191319#t004fn002" target="_blank">^a</a> cases across major types of congenital heart defect in the Pediatric Cardiac Genetic Consortium Cohort.</p

Syndromic diagnoses in the Pediatric Cardiac Genetic Consortium Cohort.

<p>Syndromic diagnoses in the Pediatric Cardiac Genetic Consortium Cohort.</p

Diagnostic types of congenital heart defect in the Pediatric Cardiac Genetic Consortium Cohort.

<p>Diagnostic types of congenital heart defect in the Pediatric Cardiac Genetic Consortium Cohort.</p

Description of nonsyndromic^a cases in the Pediatric Cardiac Genetic Consortium Cohort.

<p>Description of nonsyndromic<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191319#t003fn002" target="_blank">^a</a> cases in the Pediatric Cardiac Genetic Consortium Cohort.</p