Ref ID: 276.1
Somatic genetic events occurring in infant with neuroblastoma during the first
year of life
Gian Paolo Tonini1, Katia Mazzocco2, Raffaella Defferrari2, Simona Coco2, Luca Longo1, Patrizia Perri2,
Paola Scaruffi1, Francesca Negri3, Claudio Gambini3, Bruno De Bernardi4, Andrea Di Cataldo5
1
Laboratory of Neuroblastoma, National Institute for Cancer Research (IST), 2 Laboratory of Neuroblastoma, Italian Neuroblastoma
Foundation, 3Department of Pathology and 4Hematology/Oncology, Gaslini Children’s Hospital, Genoa, 5Department of Pediatric
Hematology/Oncology, University of Catania, Italy.
Tumor aggressiveness of neuroblastoma has mainly been associated with MYCN amplification (NMA)
and chromosome 1p36 deletion (1p36del). However, tumorigenesis of neuroblastoma remains elusive.
Tumors of infants represent a suitable natural model to identify the early events occuring in NB in a welldefined period of life. We observed 113 children with NB in the first year of life. We evaluated NMA and
1p36del by FISH, PCR-LOH analysis at 1p36 and DNA index in 97 available tumors. Moreover, CGH was
employed to identify further DNA imbalances in tumors with 1pdel. Chromosome 1pdel was found in
12/97 (12%) tumors and NMA in 9/97 (9%). Seven out of nine NMA tumors also had 1pdel. Imbalance of
chromosome 1p36 as tri-, tetra-, pentasomy but not deletion was found in 43/97 (44%) cases and a
normal pair of chromosome 1p36 was observed in 42/97 (43%). Four patients, whose tumors had 1pdel
died for disease progression; three of these had also NMA. The distribution of patients according to the
age at diagnosis showed that during the first three months of life, only 5% (2/40) tumors had 1pdel and/or
NMA; whereas, after that time the frequency of 1p36del raised up to 18% (10/57) and NMA raised up to
12% (7/57). Numerical and structural chromosome abnormalities were observed by CGH in tumors with
1p36del. Finally, four embryonal masses observed by ultrasonography had neither MNA nor 1p36del. Our
results show that in neuroblastoma of infants: a) were present both numerical and structural chromosome
abnormalities, and b) 1p36del and NMA are more frequently observed after the third month of life. Our
observation indicates that more than one mutation is occuring in the first year of life and suggests a
complex mechanism of tumorigenesis departing from both two-hit hypothesis and multistep model.
[This study is supported by Italian Neuroblastoma Foundation and AIRC]
Presentation mode(s): ORAL-PRESENTATION – PC-PROJECTOR