title: CD99 polymorphisms significantly influence the probability to develop Ewing sarcoma in earlier age and patient disease progression.
abstract: Ewing sarcoma (EWS), the second most common primary bone tumor in pediatric age, is known for its paucity of recurrent somatic abnormalities. Apart from the chimeric oncoprotein that derives from the fusion of EWS and FLI genes, recent genome-wide association studies have identified susceptibility variants near the EGR2 gene that regulate DNA binding of EWS-FLI. However, to induce transformation, EWS-FLI requires the presence of additional molecular events, including the expression of CD99, a cell surface molecule with critical relevance for the pathogenesis of EWS. High expression of CD99 is a common and distinctive feature of EWS cells, and it has largely been used for the differential diagnosis of the disease. The present study first links CD99 germline genetic variants to the susceptibility of EWS development and its progression. In particular, a panel of 25 single nucleotide polymorphisms has been genotyped in a case-control study. The CD99 rs311059 T variant was found to be significantly associated [P value = 0.0029; ORhet = 3.9 (95% CI 1.5-9.8) and ORhom = 5.3 (95% CI 1.2-23.7)] with EWS onset in patients less than 14 years old, while the CD99 rs312257-T was observed to be associated [P value = 0.0265; ORhet = 3.5 (95% CI 1.3-9.9)] with a reduced risk of relapse. Besides confirming the importance of CD99, our findings indicate that polymorphic variations in this gene may affect either development or progression of EWS, leading to further understanding of this cancer and development of better diagnostics/prognostics for children and adolescents with this devastating disease.
authors: Dept. of Experimental Diagnostics and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors: Marcella
authors: M
authors: Martinelli
authors: CRS Development of Biomolecular Therapies, Oncology Lab, Rizzoli Orthopaedic Institute, Bologna, Italy.|Experimental Oncology Lab, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors: Alessandro
authors: A
authors: Parra
authors: Dept. of Experimental Diagnostics and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors: Luca
authors: L
authors: Scapoli
authors: Dept. of Experimental Diagnostics and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors: Paola
authors: P
authors: De Sanctis
authors: CRS Development of Biomolecular Therapies, Oncology Lab, Rizzoli Orthopaedic Institute, Bologna, Italy.|Experimental Oncology Lab, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors: Valentina
authors: V
authors: Chiadini
authors: Experimental Oncology Lab, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors: Claudia
authors: C
authors: Hattinger
authors: Experimental Oncology Lab, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors: Piero
authors: P
authors: Picci
authors: Dept. of Experimental Diagnostics and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors: Cinzia
authors: C
authors: Zucchini
authors: CRS Development of Biomolecular Therapies, Oncology Lab, Rizzoli Orthopaedic Institute, Bologna, Italy.|Experimental Oncology Lab, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors: Katia
authors: K
authors: Scotlandi
mesh_terms: D000071443:12E7 Antigen / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D000071443:12E7 Antigen; C061828:CD99 protein, human
keywords: CD99; Ewing sarcoma; association analysis; polymorphisms