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Pintotable1.xlsxTable S1a. Cohort characteristicsTable S1b. Frequencies and features of TP53 variants at codon 125 in public databasesTable S1c. Annotation and interpretation of TP53 variants at codon 125 and surrounding basesTable S1d. Splice site predictionTable S1e. Primers sequences for mutagenesis constructs and cDNA sequencing Table S1f. STR profiling of Saos-2 and H1299 cell lines

S1. Proband pedigrees. S2. TP53 status as determined by Multiplex Ligation Probe Amplification for Saos-2 and H1299 cell lines. S3. TP53 altering splice variants in the (a) IARC database (b) PCGP database. (c) Total germline TP53 variants observed in IPACTR and COG studies Circles represent number of cases. S4. Chromatogram representing the constructs for the TP53 variants included in this study. S5. p53 Immunostaining of pediatric tumors associated with germline mutations at codon 125 and surrounding sequences.

Li-Fraumeni syndrome (LFS) is one of the most common cancer predisposition syndromes that affects both children and adults. Individuals with LFS are at an increased risk of developing various types of cancer over their lifetime including soft tissue sarcomas, osteosarcomas, breast cancer, leukemia, brain tumors, and adrenocortical carcinoma. Heterozygous germline pathogenic variants in the tumor suppressor gene

Early in the Coronavirus Disease 2019 pandemic, our medical center, like many, halted in-person learning activities. The narrative medicine sessions we planned for the pediatric hematology/oncology fellows were no exception. At this time we also witnessed waves of civil unrest fueled by systemic racism toward Americans of color. Amidst the isolation, apprehension, and turmoil, we turned to narrative medicine. To keep our participants safe and work around novel constraints, we adapted the narrative medicine curriculum for virtual delivery.

Li-Fraumeni syndrome (LFS) is one of the most common cancer predisposition syndromes that affects both children and adults. Individuals with LFS are at an increased risk of developing various types of cancer over their lifetime including soft tissue sarcomas, osteosarcomas, breast cancer, leukemia, brain tumors, and adrenocortical carcinoma. Heterozygous germline pathogenic variants in the tumor suppressor gene TP53 are the known causal genetic defect for LFS. Single nucleotide variants (SNVs) including missense substitutions that occur in the highly conserved DNA binding domain of the protein are the most common alterations, followed by nonsense and splice site variants. Gross copy number changes in TP53 are rare and account for less than 1% of all variants. Using next-generation sequencing (NGS) panels, we identified a paternally inherited germline intragenic duplication of TP53 in a child with metastatic osteosarcoma who later developed acute myeloid leukemia (AML). Transcriptome sequencing (RNA-Seq) demonstrated the duplication was tandem, encompassing exons 2-6 and 28 nucleotides of the untranslated region (UTR) upstream of the start codon in exon 2. The inclusion of the 28 nucleotides is expected to result in a frameshift with a stop codon 18 codons downstream of the exon 6, leading to a loss-of-function allele. This case highlights the significance of simultaneous identification of both significant copy number variants as well as SNVs/indels using NGS panels.

Although low parent health literacy (HL) has been linked to poor child health outcomes, it is not known whether differences in perceptions related to access to care and provider-parent partnership in care are potential contributing factors. We sought to assess whether parent HL is associated with differences in perceived barriers to care and attitudes regarding participatory decision-making with the provider.This was a cross-sectional analysis of data collected from parents presenting with their child to an urban public hospital pediatric clinic in New York City. Dependent variables were caregiver-reported barriers to care (ability to reach provider at night/on weekends, difficult travel to clinic) and attitudes towards participatory decision-making (feeling like a partner, relying on doctor's knowledge, leaving decisions up to the doctor, being given choices/asked opinion). The primary independent variable was caregiver HL (Short Test of Functional Health Literacy in Adults [S-TOHFLA]).A total of 823 parents were assessed; 1 in 4 (27.0%) categorized as having low HL. Parents with low HL were more likely to report barriers to care than those with adequate HL: trouble reaching provider nights/weekends, 64.9% vs. 49.6%, (p0.001, adjusted odds ratio [AOR] 1.7, 95% confidence interval [95% CI] 1.2-2.4); difficult travel, 15.3% vs. 8.0%, (p = 0.004, AOR 1.8, 95% CI 1.1-3.0). Low HL was also associated with not feeling like a partner (28.8% vs. 17.1%; AOR 2.0; 95% CI 1.4-3.0), preference for relying on the doctor's knowledge (68.9% vs. 52.2%; AOR 1.7; 95% CI 1.2-2.4), and preference for leaving decisions up to the doctor (57.7% vs. 33.3%; AOR 2.2; 95% CI 1.6-3.1).Addressing issues of parent HL may be helpful in ameliorating barriers to care and promoting provider-parent partnership in care.