Increased copy number of the DLX4 homeobox gene in breast axillary lymph node metastasis.

DLX4 is a homeobox gene strongly implicated in breast tumor progression and invasion. Our main objective was to determine the DLX4 copy number status in sentinel lymph node (SLN) metastasis to assess its involvement in the initial stages of the axillary metastatic process. A total of 37 paired samples of SLN metastasis and primary breast tumors (PBT) were evaluated by fluorescence in situ hybridization, quantitative polymerase chain reaction and array comparative genomic hybridization assays. DLX4 increased copy number was observed in 21.6% of the PBT and 24.3% of the SLN metastasis; regression analysis demonstrated that the DLX4 alterations observed in the SLN metastasis were dependent on the ones in the PBT, indicating that they occur in the primary tumor cell populations and are maintained in the early axillary metastatic site. In addition, regression analysis demonstrated that DLX4 alterations (and other DLX and HOXB family members) occurred independently of the ones in the HER2/NEU gene, the main amplification driver on the 17q region. Additional studies evaluating DLX4 copy number in non-SLN axillary lymph nodes and/or distant breast cancer metastasis are necessary to determine if these alterations are carried on and maintained during more advanced stages of tumor progression and if could be used as a predictive marker for axillary involvement.

SF-1 overexpression in childhood adrenocortical tumours.

The steroidogenic factor 1 (SF-1) gene encodes a transcription factor playing a pivotal role in the regulation of adrenogenital development. We have recently shown that SF-1 is amplified in childhood adrenocortical tumours (ACT). This study was aimed to assess if an increase in SF-1 gene copy number was associated with increased protein levels and to study the correlation between SF-1 expression and ACT clinical parameters. An increased SF-1 copy number was detected in eight of the 10 ACT cases studied. Conversely, the SF-1 protein was found to be overexpressed in all cases, compared to normal age-matched adrenal glands. No significant correlation was found between SF-1 protein levels and its gene copy number. Furthermore, no significant correlation existed with histological grade or with the clinical manifestation or evolution of disease. This data show that SF-1 overexpression is widespread in childhood ACT and is likely to play a role in its pathogenesis.

Neuroblastoma in southern Brazil: an 11-year study.

The authors report on the incidence and clinical characteristics of neuroblastoma in southern Brazil. The aims of the study were to evaluate the age at diagnosis, tumor stage, MYCN status, and tumor histopathology, and to relate these factors to survival. All patients with neuroblastoma, 15 years old or younger (n = 125), admitted to the three major pediatric oncology hospitals in the state of Parana over a period of 11 years (between January 1990 and December 2000), were included in the analysis. All patients were followed for at least 5 years. In addition, a FISH evaluation for MYCN status was conducted in a subset of 34 tumors. Overall survival for tumor stages 1, 2, 3, and 4 was 100%, 72%, 59%, and 17%, respectively. Sixty-two percent (77/125) of all patients were older than 2 years; these represented 71% (57/80) of the patients with stage 4 disease. Children who presented with an unfavorable histopathology had a significantly worse prognosis (20% survival) than children with a favorable histopathology (67% survival). MYCN amplification was detected most commonly in stages 3 and 4 tumors (13/16). These data showed a delayed diagnosis of neuroblastoma in children in southern Brazil, and consequently survival was considerably lower in these patients.

Amplification of the steroidogenic factor 1 gene in childhood adrenocortical tumors.

Southern Brazil has one of the highest incidences of childhood adrenocortical tumors (ACTs), occurring 10-15 times more frequently than worldwide estimates. The reasons for this increase remain elusive. In an attempt to further characterize the genetic changes in childhood ACTs, we recently detected a consistent gain of 9q (or a portion of it) in eight of nine cases of pediatric ACTs and amplification of 9q34 in the majority of these cases using comparative genomic hybridization. Other studies involving both childhood and adult ACTs have corroborated these findings. To follow up on these results, we examined whether the steroidogenic factor 1 (SF-1) gene, which is located in this chromosomal region and plays an important role in the development and function of the adrenal cortex is amplified in these ACT cases. We detected increased copy number of the SF-1 gene in all eight cases with 9q gain, suggesting an association between an increased copy number of the SF-1 gene and adrenocortical tumorigenesis.

High frequency of t(12;21)(p13;q22) in children with acute lymphoblastic leukemia and known clinical outcome in southern Brazil.

The presence of the t(12;21)(p13;q22) distinguishes a subset of children with acute lymphoblastic leukemia (ALL) that present a favorable prognosis. This is a cryptic translocation difficult to detect through conventional cytogenetics. In this study, bone marrow samples from 30 children with ALL from southern Brazil were evaluated by fluorescence in situ hybridization (FISH) for the t(12;21), using locus specific probes to detect the TEL/AML1 rearrangement. The selection criteria included: age (0-12 years old); FAB classification (L1 or L2), absence of specific clonal chromosomal aberrations; and adequate cellular integrity to perform FISH analysis. A frequency of 40% of the t(12;21) was observed, in addition to extra copies of the AML1 gene in 7.5% of patients. These findings were analyzed in relation to the patient's clinical parameters and compared with other pediatric populations.

Comprehensive cytogenetic evaluation of a mature ovarian teratoma case.

Mature ovarian teratomas are benign ovarian germ cell tumors that usually present with a normal karyotype. There are very few reports describing chromosomal abnormalities in these tumors, none of which are recurrent. In this study we report on a mature teratoma case with clonal chromosomal alterations which include monosomies of chromosomes 6, 14, 16, and 21; trisomies of chromosomes 14 and 21; and deletions of Xq, 5p, 16p, and 17p. Comparative genomic hybridization evaluation of the sample revealed a normal profile. These findings are discussed together with the cytogenetic reports on other cases of ovarian teratomas described in the literature.