Although several genes have been investigated in adrenal tumorigenesis, the genetic background of adrenocortical tumors (ACT) remains poorly characterized. In southern Brazil, the annual incidence of ...ACT is unusually high, ranging from 3.4-4.2/million children, compared with a worldwide incidence of 0.3/million children younger than 15 yr. Environmental factors have been implicated because the distribution of these tumors follows a regional, rather than a familial, pattern. However, decreased penetrance of a particular gene defect cannot be excluded. Because linkage or other traditional genetic analyses would not be appropriate to investigate the defect(s) associated with ACT in this population, we used comparative genomic hybridization (CGH) to screen for DNA sequence copy number changes in 9 nonfamilial ACT (6 carcinomas and 3 adenomas) from unrelated patients from this region. Six female (aged 10 months to 6 3/4 yr) and 3 male (1 1/12 to 3 1/4 yr) patients were studied. Three carcinomas were at stage I, 1 was at stage II, and another was at stage III. Two carcinomas had evidence of invasion of the vena cava, and 3 were more than 3 cm in size. All patients underwent surgical excision of their tumors; chemotherapy was administered to cancer patients. Currently, all patients are alive and in remission, with the exception of 1 patient with stage III cancer. High mol wt DNA was extracted from tumor tissue obtained at surgery and frozen at -70 C. This DNA was labeled and used for CGH according to standard procedures. Digital image analysis was performed to detect chromosomal gains or losses. CGH evaluation revealed extensive genetic aberrations in both adenomas and carcinomas; there were no significant differences relative to age, gender, size, or stage of the tumor (P > 0.1). Chromosomes and chromosomal regions 1q, 5p, 5q, 6p, 6q, 8p, 8q, 9q, 10p, 11q, 12q, 13q, 14q, 15q, 16, 18q, 19, and 20q demonstrated gains, whereas 2q, 3, 4, 9p, 11, 13q, 18, 20p, and Xq showed losses. The most striking finding was consistent copy number gain of chromosomal region 9q34 in 8 of the 9 tumors. We conclude that both benign and malignant ACT from southern Brazil show multiple genetic aberrations, including a consistent gain of chromosomal region 9q34. This genomic area may harbor genetic defects that predispose to ACT formation and are shared by the patients who were investigated in this study or are accumulated epigenetically under the influence of a common factor, such as an environmental mutagen.
The objective of this study was to determine the contribution of a familial history of cancer (FHC) to the development of leukemia in children below 2 years of age. This is a national hospital-based ...case–control study of children 0–24 months of age recruited from 15 Brazilian hospitals from several regions providing oncological care and local general hospitals. Participants’ FHC antecedents were obtained through face-to-face interviews with the mothers of cases and controls using a standardized questionnaire. Unconditional logistic regression was used to determine crude and adjusted (adj.) odds ratios (OR), and the respective 95 % confidence intervals (CI), of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) after adjustment for selected variables. FHC antecedents were obtained from 178 ALL, 51 AML, and 428 controls. FHC in second-degree relatives (grandparents, uncles, cousins) showed an adj. OR=1.66 (95% CI 1.12–2.45) for ALL. Antecedents of two or more relatives with cancer showed a statistically significant two-fold higher risk of either ALL or AML. Paternal, and joint paternal and maternal antecedents of cancer also showed statistically significant higher adj. OR, respectively: 1.80 and 1.89 for ALL, and 2.34 and 3.23 for AML. Hematological malignancies among second-degree relatives showed an adj. OR=3.48 (95% CI 1.72–7.09) for ALL. According to the anatomic site, antecedents of leukemia/lymphoma among case relatives, compared with the control ones, showed an OR=2.98 (95% CI 1.52–5.82) for ALL, whereas stomach cancer antecedents showed an OR=3.55 (95% CI 1.02–12.39) for AML. The observed results support the hypothesis that FHC antecedents are associated with leukemogenesis in children below 2 years of age.
Although several genes have been investigated in adrenal tumorigenesis,
the genetic background of adrenocortical tumors (ACT) remains poorly
characterized. In southern Brazil, the annual incidence of ...ACT is
unusually high, ranging from 3.4–4.2/million children, compared with a
worldwide incidence of 0.3/million children younger than 15 yr.
Environmental factors have been implicated because the distribution of
these tumors follows a regional, rather than a familial, pattern.
However, decreased penetrance of a particular gene defect cannot be
excluded. Because linkage or other traditional genetic analyses would
not be appropriate to investigate the defect(s) associated with ACT in
this population, we used comparative genomic hybridization (CGH) to
screen for DNA sequence copy number changes in 9 nonfamilial ACT (6
carcinomas and 3 adenomas) from unrelated patients from this region.
Six female (aged 10 months to 6 3/4 yr) and 3 male (1 1/12 to 3 1/4 yr)
patients were studied. Three carcinomas were at stage I, 1 was at stage
II, and another was at stage III. Two carcinomas had evidence of
invasion of the vena cava, and 3 were more than 3 cm in size. All
patients underwent surgical excision of their tumors; chemotherapy was
administered to cancer patients. Currently, all patients are alive and
in remission, with the exception of 1 patient with stage III cancer.
High mol wt DNA was extracted from tumor tissue obtained at surgery and
frozen at −70 C. This DNA was labeled and used for CGH according to
standard procedures. Digital image analysis was performed to detect
chromosomal gains or losses. CGH evaluation revealed extensive genetic
aberrations in both adenomas and carcinomas; there were no significant
differences relative to age, gender, size, or stage of the tumor
(P > 0.1). Chromosomes and chromosomal regions 1q,
5p, 5q, 6p, 6q, 8p, 8q, 9q, 10p, 11q, 12q, 13q, 14q, 15q, 16, 18q, 19,
and 20q demonstrated gains, whereas 2q, 3, 4, 9p, 11, 13q, 18, 20p, and
Xq showed losses. The most striking finding was consistent copy number
gain of chromosomal region 9q34 in 8 of the 9 tumors. We conclude that
both benign and malignant ACT from southern Brazil show multiple
genetic aberrations, including a consistent gain of chromosomal region
9q34. This genomic area may harbor genetic defects that predispose to
ACT formation and are shared by the patients who were investigated in
this study or are accumulated epigenetically under the influence of a
common factor, such as an environmental mutagen.
A doença de Gaucher (DG) é um erro inato do metabolismo do grupo das doenças lisossômicas de depósito, sendo a mais freqüente do referido grupo. É de herança autossômica recessiva, portanto com risco ...de 25% a cada gestação de casal heterozigoto. A doença é resultante da deficiência da beta-glicosidase ácida ou beta-glicocerebrosidase, que leva ao acúmulo de glicolipídios nos macrófagos principalmente em baço, fígado, medula óssea e pulmão. As manifestações clínicas ou fenotípicas da DG vão depender do grau de deficiência da enzima, existindo três tipos: Tipo I, forma não neuropática, afeta crianças e adultos com hepatoesplenomegalia, anemia, trombocitopenia, leucopenia e lesões ósseas; Tipo II, forma neuropática aguda, afeta crianças com 4-5 meses com quadro neurológico grave, hepatoesplenomegalia e comprometimento pulmonar e o Tipo III, forma neuropática crônica, afeta crianças e adolescentes com quadro neurológico menos grave que o Tipo II e ainda pode comprometer fígado, baço e ossos. Um grupo de catorze médicos com experiência no tratamento da DG com reposição enzimática realizaram extensa revisão da literatura, confrontaram com os dados evolutivos dos pacientes brasileiros e chegaram a um consenso quanto aos critérios para iniciar o tratamento, a dose da enzima e freqüência das infusões, do acompanhamento ambulatorial, laboratorial e radiológico. O Grupo Brasileiro de Estudos em Doença de Gaucher e outras Doenças de Depósito Lisossômico (GBDDL) tem o objetivo de estabelecer diretrizes para o diagnostico, tratamento e acompanhamento de pacientes com doença de Gaucher no Brasil. Esta iniciativa pioneira visa uniformizar a conduta no país com relação ao tratamento de DG com reposição enzimática, tratamento de alto custo porém de grande eficácia.
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