Abstract / Summary
Background: Constitutional trisomy 8 mosaicism (CT8M) is a rare chromosomal disorder with poorly characterized cancer risk. This systematic review aimed at summarizing reported cases of malignancy and associated clinical outcomes in individuals with CT8M.
Methods: A systematic literature search was conducted in PubMed, Scopus, Web of Science, Ichushi, and Google Scholar up to January 30, 2026, without restrictions on language and publication date. Case reports and case series reporting individuals with confirmed CT8M and malignancies were included. JBI Critical Appraisal Checklists were used to evaluate the quality of included studies. Data synthesis involved a descriptive approach.
Results: Thirty-seven studies describing 47 individuals with CT8M and tumors were identified. A female predominance was observed (25/45, 55.5%), and age at malignancy diagnosis ranged from 1 to 84 years, with most cases occurring in childhood or adolescence. Over half of the individuals had a normal appearance (52.3%), while approximately one third exhibited a typical CT8M phenotype (28.5%). Hematologic malignancies predominated (82.9%), particularly, myelodysplastic syndromes (MDS) and acute myeloid leukemia. Importantly, 27.2% of individuals with MDS showed isolated trisomy 8 in bone marrow without additional cytogenetic abnormalities. Solid tumors were less frequent and were predominantly embryonal. Clinical outcomes were generally poor, and phenotypic severity or tissue-specific mosaic percentages did not appear to correlate with outcomes.
Conclusions: Our findings suggest a distinctive cancer profile characterized by a marked predominance of myeloid neoplasms, often with an onset several decades earlier than expected and in the absence of overt syndromic features. The observed pattern may reflect the biological consequences of increased gene dosage and transcriptional dysregulation associated with constitutional trisomy 8, although the underlying mechanisms remain uncertain. Targeted evaluation for CT8M may be particularly relevant in (i) pediatric patients with MDS, (ii) individuals with persistent trisomy 8 in bone marrow or peripheral blood with planned therapeutic interventions, and (iii) patients with subtle dysmorphic features rather than through universal screening approaches.