Partial trisomy of 2p and neuroblastoma

To the Editor:

We read with interest the report of a patient with partial trisomy 2p (p23-pter) in a recent issue of this Journal [Al-Saffar et al., 2000]. Although not cited by these authors, we published a report in 1997 of a patient with partial trisomy 2p resulting from a de novo unbalanced translocation der(13)t(2;13)(p23;q34)[Patel et al., 1997]. The cytogenetic breakpoint on chromosome 2 in our patient, band p23, was apparently the same as in the case presented by Al-Saffar et al. [2000]. Our patient died at age 17 months from neuroblastoma. We showed, using FISH with the cosmid cloned probe pNb101, that the duplication included the NMYC locus at 2p23-4 in our patient. Two previously reported cases of 2p duplications also developed neuroblastomas [Nagano et al., 1980; Say et al., 1980]. FISH studies have shown that the N-myc proto-oncogene may be duplicated at its resident site (2p23-4) in neuroblastoma cell lines, which lack amplification [Corvi et al., 1995]. This has suggested that duplication of N-myc may precede amplification or represent an alternative mechanism of N-myc activation.

We were surprised that the risk of neuroblastoma was not mentioned in the table of clinical features or elsewhere in the text of Al-Saffar et al.'s report [Al-Saffar et al., 2000]. In view of the risk of development of neuroblastoma in the presence of germline duplication of NMYC, we consider it appropriate to screen for duplication of this locus as part of the cytogenetic work up of patients with duplications involving this region of chromosome 2.