Aberrations of p16INK4A, p14ARF and p15INK4B genes in pediatric solid tumors

Expression of the p16(INK4A) (p16), p15(INK4B) (p15), and p14(ARF) genes, located at 9p21, was examined in pediatric neuroblastoma (NB), Ewing's sarcoma (ES), and rhabdomyosarcoma (RMS). p16 expression was absent in 4 of 5 ESs, and 2 of these 4 cases died. p16 expression was reduced or absent in 10 of 12 RMSs, and 4 of these 10 cases died. These results suggested the possibility that p16 expression was associated with the progression of ES and RMS. There has been no previous report on p14(ARF) in NB. Our investigation might indicate that abnormal expression of the p16 and p14(ARF) was associated with a poor prognosis in NB, although in some cases of NB normal p16 and abnormal p14(ARF) expression was seen. These findings suggest an important role of P14(ARF) gene in the tumorigenesis of NB. The different incidence of expression of the p16, p15, and p14(ARF) genes in these 3 tumor types may reflect differences of the molecular process through which the 3 tumors develop. Our results suggest that abnormal expression of the p16 and/or p14(ARF) may be associated with a poor prognosis in these 3 tumors.