RB1 mutation

Although genetic testing was not performed, bilateral disease strongly suggests germline RB1 mutation, a well-established risk factor for osteosarcoma. Persistent musculoskeletal symptoms in such patients warrant prompt radiologic evaluation to avoid diagnostic delay.

Furthermore, our results highlight the importance of offering targeted genetic testing and counseling to families with RB1 mutations. The identification of the somatic origin of this mutation was vital in ruling out the heritability of this condition in this specific patient.

Using a large-scale Japanese genomic panel dataset, we characterized the molecular alterations associated with S/DD. S/DD frequently exhibits low Nectin-4 expression and basal-like molecular features, which may have implications for treatment selection and inform future therapeutic strategies.

Although mice with Rb1 gene inactivation invariably develop pituitary adenomas, and some evidence suggests that a subset of pituitary adenomas have lack or reduced expression of Rb protein, to date no evidence has been reported that patients with germline mutations in the RB1 gene (that encodes for Rb protein) are at risk of developing pituitary adenomas. Here, we report the case of a patient with childhood (age 1 year) onset retinoblastoma because of a germline pathogenic variant of the RB1 gene who presented with a somatotropinoma diagnosed at a young age (20) and whose pituitary adenoma cells showed loss of expression of Rb protein by immunohistochemistry, suggesting a role of Rb in preventing the development of pituitary adenomas.

Survivors of hereditary retinoblastoma, caused by germline mutations in the RB1 gene, have a substantially increased risk of developing benign and malignant lipomatous tumors including atypical spindle cell/pleomorphic lipomatous tumor and dysplastic lipoma. This report describes the MRI findings of several such lesions in a survivor of bilateral retinoblastoma including features such as enhancement that might otherwise be concerning for higher-grade malignancy.

Taken together, the repertoire of genetic alterations in primary and metastatic/recurrent MPTs shows overlap, and CDKN2A/2B homozygous deletions may play a role in progression. Additionally, molecular profiles of MPTs may vary according to genetic ancestry and MED12 mutational status.

MTAP-deleted thoracic tumors exhibit reproducible clinical and molecular features across populations. Our findings support the rational, globally applicable development of MTAP-targeted synthetic lethal strategies in thoracic malignancies, particularly in combination with molecular targeted agents.

Single-cell RNA-seq (scRNA-seq) analysis confirmed the specific enrichment of signature genes within malignant cells, and coexpression network analysis (hdWGCNA) further linked the high-risk phenotype to transcriptional modules. In conclusion, we established and validated a robust metabolic gene signature that not only predicts prognosis but also delineates a high-risk GBM subtype defined by integrated metabolic, immunogenomic, and transcriptional features, providing new insights into the determinants of GBM aggressiveness.

In this study, the genomic landscape of early-stage p16 + OPX shows comparable mutational frequencies of known genes in advanced/metastatic stages, including PIK3CA, FGFR3, and FBXW7. This early-stage cohort contained higher-than-expected RB1 and KMT2D mutations.

IDH1 mutations were associated with global transcriptional repression and evidence of metabolic and epigenetic reprogramming. These results depict IDH-mutant prostate cancer as a subtype that can present with high tumor stage and grade, but is associated with favorable outcomes.

When the all-cancers results were pooled with those from an earlier study of very largely the same cohort with non-overlapping follow-up, the estimated lifetime SIR for non-ocular cancer among mutation-carrier parents after the birth of their affected child was 4.32 (95% CI 3.06-5.93). Our results confirm that parents who themselves had retinoblastoma have an increased risk of subsequent cancers, and parents who are not mutation carriers have a risk similar to the general population.

However, these tumors lacked RB1 mutation and likely inactivate RB1 through HPV's known capacity to promote post-translational degradation of RB1 protein. These data suggest that the two most common subtypes of cutaneous SCC proceed through distinct pathways of molecular pathogenesis and highlight an unexpected relationship between Bowenoid and HPV-associated cutaneous SCC.