Presence of 1q gain and absence of 7p gain are new predictors of local or metastatic relapse in localized resectable neuroblastoma

Abstract

We have addressed the search of novel genetic prognostic markers in a selected cohort of patients with stroma-poor localized resectable neuroblastoma (NB) who underwent relapse or progression (group 1) or complete remission (group 2) over a minimum follow-up of 32 months from diagnosis. Twenty-three Italian patients with localized resectable NB (stages 1 and 2) diagnosed from 1994 through 2005 were studied. All patients received surgical treatment. Chemotherapy was administered only to the three stage 2 patients who had MYCN-amplified tumors. High-resolution array-comparative genomic hybridization (CGH) DNA copy-number analysis technology was used to identify novel prognostic markers. Chromosome 1p36.22p36.32 loss and 1q22qter gain, detected almost exclusively in group 1 patients, were significantly associated with poor event-free survival (EFS) (p = 0.0024 and p = 0.024, respectively). In contrast, patients with 7p11.2p22 gain, who belonged predominantly to group 2, had a significantly better EFS (p = 0.015). The frequency of 17q gain or 3p and 11q losses did not differ significantly in group 1 versus group 2 NBs. The sensitive technique allowed us to define the smallest region of 1p deletion. In conclusion, 1q22qter gain and 7p11.2p22 gain might represent new prognostic markers in localized resectable NB, but the small study size and the retrospective nature of the findings warrant further validation of the results in larger studies.

Fig. 1

Overall survival (A) and event-free survival (B) for 23 localized group 1 and group 2 resectable neuroblastoma patients.

Fig. 2

(A) Summary of the patterns of total gains (right, green lines) and losses (left, red lines) detected in 23 localized resectable neuroblastoma samples using array-comparative genomic hybridization (CGH). (B) Aberration patterns present in group 1 tumors. (C) Aberration patterns present in group 2 tumors. Each line represents a copy number aberration in the individual tumors. The thick lines indicate the number of tumors, shown above the lines, with the same imbalances. The arrows indicate the major differences between the two CGH results.

Fig. 3

Median number of structural copy number aberrations (CNAs) per tumor in the two groups of patients (group 1, relapsed tumors; group 2, nonrelapsed tumors). Mann-Whitney U-test, p = 0.016.

Fig. 4

(A) Minimal common region of 1p loss. The arrow points to the break point position on chromosome 1p. (B–D) Event-free survival according to chromosome 1p loss (B), chromosome 1q gain (C), and chromosome 7p gain (D).