9p21.3 Microdeletion involving CDKN2A/2B in a young patient with multiple primary cancers and review of the literature.

Germline pathogenic variants in predispose to various cancers, including melanoma, pancreatic cancer, and neural system tumors, whereas variants are associated with renal cell carcinoma. A few case reports have described heterozygous germline deletions spanning both and associated with a cancer predisposition syndrome (CPS) that constitutes a risk of cancer beyond those associated with haploinsufficiency of each gene individually, indicating an additive effect or a contiguous gene deletion syndrome. We report a young woman with a de novo germline 9p21 microdeletion involving the / genes who developed six primary cancers since childhood, including a very rare extraskeletal osteosarcoma (eOS) at the age of 8. To our knowledge this is the first report of eOS in a patient with / deletion.