Cytogenetic and molecular study of two human neuroblastoma cell lines.

Long-term cell cultures (GI-LA-N and GI-ME-N) were established from the metastases of two disseminated neuroblastomas (NB). The first was obtained from a lymph node biopsy of a stage III NB after 7 months of chemotherapy, and the second from a bone marrow specimen of a stage IV NB after 6 months of chemotherapy. Cytogenetic investigation revealed several structural and numerical alterations in both cell cultures, but the only common chromosomal aberration was partial monosomy of 1p. Moreover, at the 5th in vitro passage, GI-LA-N displayed a high number of double minutes, not seen in GI-ME-N even after 33 subcultures. Molecular analysis revealed N-myc oncogene amplification in GI-LA-N cells, whereas, only one copy was found in GI-ME-N. No structural N-myc rearrangement was detected in either cell culture.

Antiblastic treatment does not affect N-myc gene amplification in neuroblastoma.

Gene amplification has been found in the genome of cells growing in vivo and/or in vitro. In cell lines with acquired multidrug resistance gene amplification has been frequently detected. Moreover, extra-copies of cellular oncogenes have been located in tumor cells in vivo; particularly N-myc gene amplification was discovered in advanced stage of neuroblastoma (NB). Neuroblastoma, a tumor of neural origin, has a high incidence in children. N-myc amplification has been demonstrated in untreated patient and a positive significant correlation with the progression of the disease has been established. In this paper we report on four NB patients treated with a polychemotherapeutic protocol and showing N-myc amplification. One patient examined before and after treatment displayed a slight change in N-myc gene copy numbers. It was shown that N-myc gene amplification is not affected by drug activities and that minimal residual of cells bearing N-myc amplification may remain in the tumor mass. N-myc amplification can also cause advantageous cell growth in the presence of drugs. The implications in the pharmacologic management of NB patient showing N-myc gene amplification is discussed.

[Amplification of the N-myc cellular oncogene in neuroblastoma. Relation to other tumor markers]. / Amplificazione dell'oncogene cellulare N-myc nel neuroblastoma. Relazione con altri markers tumorali.

N-myc oncogene is amplified in several human neuroblastoma cell lines and fresh neoplastic tissues; amplification would be highly correlated with advanced stages of neoplasia and associated with poor outcome of the disease. According to these data, N-myc amplification should be a new prognostic marker in addition to classical clinical and laboratory findings commonly monitored in neuroblastoma; some of them are levels of urinary Vanillylmandelic Acid (VMA) and Homovanillic Acid (HVA), serum Lactic Dehydrogenase (LDH) and serum Ferritin (sFe). We studied 4 patients in stage III and IV; N-myc amplification was detected in 2 cases in stage IV in primary tumor cells and in one case this finding was associated with high levels of serum Ferritin and LDH, while no correlation between other laboratory parameters and N-myc amplification has been found. We propose that N-myc amplification has to be evaluated with other prognostic factors to obtain useful information about the disease and the survival of the patient.

N-myc oncogene amplification in a patient with IV-S neuroblastoma.

Neuroblastoma (NB) is a tumor usually arising in children and young adults showing different degrees of malignancy. Recently, the presence of N-myc amplification in neuroblasts has been associated with a poor outcome in the late stages of disease (Evans's Stage IV). Until now no amplification of N-myc gene has been observed in Stage IV-S, usually considered to have a favorable prognosis. In this paper we report a case of a child affected by NB Stage IV-S showing mild N-myc gene amplification. The finding of N-myc amplification in our patient shows that such alteration of the N-myc oncogene is not necessarily correlated with a poor prognosis; in this light the role of N-myc amplification in the neoplastic process should be reconsidered.