Multimodal Cytogenetic and Molecular Approach for the Detection of a Constitutional Balanced Paracentric Inversion Disrupting <i>RB1</i> in an Infant With Bilateral Retinoblastoma

Genes Chromosomes and Cancer · 2026-04-01

We report a case of hereditary bilateral retinoblastoma due to a de novo germline inversion on chromosome 13, resulting in disruption of the RB1 gene. The patient is a 22-month-old female who initially presented to the emergency room at 11 months of age with an erythematous left eye and leukocoria of the right eye. Computed tomography (CT) of the brain and orbits showed solid internal calcifications arising from the posterior globes concerning for bilateral retinoblastoma. Magnetic resonance imaging (MRI) of the brain and orbits confirmed bilateral retinoblastoma without associated pineal region or suprasellar mass. On initial examination under anesthesia, the right eye showed one tumor in the macula and two tumors in the inferior mid-periphery. Sub-retinal seeding extended to the inferior periphery. The left eye was enucleated and pathology showed leptomeningeal extension along the optic nerve extending to the surgical margin. The patient was treated on a non-protocol treatment plan with five cycles of vincristine, carboplatin, etoposide, cyclophosphamide, and weekly intraventricular topotecan via Ommaya reservoir, followed by autologous stem cell rescue. Tumor analysis showed loss of pRB protein expression by immunohistochemistry and methylation copy number profiling showed several segmental gains and losses, including focal loss of RB1 on 13q. A 123-gene cancer predisposition germline panel using genome and exome sequencing initially did not identify any RB1 single nucleotide variants or insertion/deletions. Subsequent constitutional chromosome analysis for RB1 showed a paracentric inversion between bands 13q14.2 and 13q31. Optical genome mapping (OGM) showed that the proximal breakpoint of the balanced inversion at 13q14.2 was within intron 17 of RB1, while the distal breakpoint at 13q31.3 did not interrupt any known genes of clinical significance. We review the various molecular techniques that aided in diagnosis of this patient and provide a summary of similar RB1-disrupting structural variants reported in the literature.

Characterization of Genetic Etiological Factors for Pediatric Acute Lymphoblastic Leukemia in Large Childhood Cancer Survivorship Cohorts

Figshare · 2026-04-16

GWAS summary statistics for the study “Characterization of Genetic Etiological Factors for Pediatric Acute Lymphoblastic Leukemia in Large Childhood Cancer Survivorship Cohorts.”Support for this research is provided by the National Cancer Institute (R01 CA283333, R01 CA230631) and the American Lebanese Syrian Associated Charities (ALSAC). The St. Jude Lifetime Cohort (SJLIFE) study is supported by the National Cancer Institute at the National Institutes of Health (U01 CA195547). The Childhood Cancer Survivor Study (CCSS) is supported by the National Cancer Institute (U24 CA055727).

Characterization of Genetic Etiological Factors for Pediatric Acute Lymphoblastic Leukemia in Large Childhood Cancer Survivorship Cohorts

Figshare · 2026-04-16

GWAS summary statistics for the study “Characterization of Genetic Etiological Factors for Pediatric Acute Lymphoblastic Leukemia in Large Childhood Cancer Survivorship Cohorts.”Support for this research is provided by the National Cancer Institute (R01 CA283333, R01 CA230631) and the American Lebanese Syrian Associated Charities (ALSAC). The St. Jude Lifetime Cohort (SJLIFE) study is supported by the National Cancer Institute at the National Institutes of Health (U01 CA195547). The Childhood Cancer Survivor Study (CCSS) is supported by the National Cancer Institute (U24 CA055727).

Reply to: Beyond Parametric Assumptions: Unsupervised Methods Enhance DNA Repair Gene Discovery in <i>SMARCAL1</i> Identification

Journal of Clinical Oncology · 2026-03-12

SOMATIC UBA1 MUTATIONS IN PEDIATRIC MDS/AML: FIRST CASES SUGGEST DISTINCT PATHOGENESIS FROM ADULT VEXAS SYNDROME

Blood Neoplasia · 2026-04-01

Supplemental Table 2 from Contribution of Germline Predisposition to Pediatric Thyroid Cancer

2025-09-02

&lt;p&gt;Supplemental Table 2. Genes included on multigene panel tests.&lt;/p&gt;

Supplemental Table 3 from Contribution of Germline Predisposition to Pediatric Thyroid Cancer

2025-09-02

&lt;p&gt;Supplemental Table 3. Total cohort of 78 Patients with thyroid carcinoma, including those who did and did not undergo genetic testing.&lt;/p&gt;

Inferring germline pharmacogenomics from tumor transcriptome

Pharmacogenetics and Genomics · 2025-09-25

OBJECTIVES: Pharmacogenomic testing is rapidly becoming the standard of care in treating pediatric acute lymphoblastic leukemia (ALL). Risk classification of ALL can be performed through whole transcriptome sequencing (WTS) of diagnostic tumor samples. We evaluated the feasibility of inferring germline pharmacogenomic genotypes from the tumor transcriptome in ALL. METHODS: Transcriptome and paired tumor-germline genome sequencing data were collected from clinical testing at St. Jude Children's Research Hospital. Genotypes for pharmacogenes that are actionable for medications used in the management of pediatric ALL ( TPMT, NUDT15 , and G6PD ) were determined using a rule-based algorithm from transcriptome data. WTS-derived genotype calls were compared with germline genotypes obtained from whole genome sequencing (WGS) and clinical genotyping assays. RESULTS: Among 650 patients with ALL, 36 (5.5%) patients had somatic copy number loss on chromosomes 6, 13, or X, where TPMT , NUDT15 , and G6PD are located, respectively. For the remaining 614 patients, WTS provided thiopurine dosing guidance by calling both TPMT and NUDT15 diplotypes in 545 patients (83.8%). For G6PD , accurate genotyping was called for 367 male patients. We observed a greater than 99% concordance between tumor WTS and germline WGS diplotypes for all three genes. CONCLUSION: The leukemia transcriptome can be used to provide accurate genotyping calls for select germline pharmacogenes actionable in the treatment of pediatric ALL.

Supplemental Table 4 from Contribution of Germline Predisposition to Pediatric Thyroid Cancer

2025-09-09

&lt;p&gt;Supplemental Table 4. Patient Cancer and Treatment History.&lt;/p&gt;

Supplemental Table 3 from Contribution of Germline Predisposition to Pediatric Thyroid Cancer

2025-09-09

&lt;p&gt;Supplemental Table 3. Total cohort of 78 Patients with thyroid carcinoma, including those who did and did not undergo genetic testing.&lt;/p&gt;