Sylvia Satomi Takeno

O Carcinoma Basocelular (CBC) é o tipo de câncer de pele mais comum, originado a partir de células basais epiteliais que perdem suas funções normais de diferenciação e queratinização. Este estudo explorou a relação entre Variantes de Polimorfismo de Nucleotídeo Único (SNPs), especificamente rs121434569 e rs121434568, no gene do Receptor do Fator de Crescimento Epidérmico (EGFR), e sua associação com o desenvolvimento do CBC. Em um exame abrangente de 142 amostras de tecido parafinado de pacientes da Paraíba com diagnóstico histopatológico de CBC, as amostras foram submetidas à extração de DNA e PCR estendida específica para alelos. A análise revelou que as frequências genotípicas observadas dos SNPs estavam em desequilíbrio de Hardy-Weinberg, sendo o valor Qui-Quadrado para rs121434569 igual a 76,92 (P=0,001) e para rs121434568 igual a 11,56 (P=0,0054), indicando significância estatística com P<0,05. As observações confirmam que a expressão e a atividade alterada do EGFR, influenciadas pelas mutações pontuais nos SNPs investigados, desempenham um papel crucial na patogênese do CBC. O método utilizado conseguiu identificar com precisão os genótipos através das temperaturas de fusão específicas. Esta pesquisa ressalta a importância das alterações no EGFR, especialmente a mutação L858R, que causa ativação constitutiva do receptor, contribuindo para o crescimento celular descontrolado observado no CBC.

This study evaluated the presence of Human Papillomavirus (HPV) and Bovine Leukemia Virus (BLV) DNA in breast cancer (BC) samples from women in Northeastern Brazil. We analyzed 186 formalin-fixed, paraffin-embedded tissue block samples using PCR and qPCR to detect HPV and BLV DNA. BLV DNA was not detected in any BC patients. However, HPV DNA was found in 46.2\% of the BC samples: 44.6\% were positive for HPV16, 3.5\% for HPV31, and 2\% were coinfected with HPV16 and HPV31. Additionally, we found an association between HPV-positive BC and Ki-67 expression (P=0.03, OR=1.85; CI=1.02-3.34), as well as between HPV31-positive BC and mitotic index (P=0.047). Although BLV was not detected in BC patients from Northeastern Brazil, the association between HPV and cell proliferation markers warrants further investigation, as HPV may contribute to the aggressiveness of BC in these patients.

Trisomy 9p is one of the most common partial trisomies found in newborns. We report the clinical features and cytogenomic findings in five patients with different chromosome rearrangements resulting in complete 9p duplication, three of them involving 9p centromere alterations. The rearrangements in the patients were characterized by G-banding, SNP-array and fluorescent in situ hybridization (FISH) with different probes. Two patients presented de novo dicentric chromosomes: der(9;15)t(9;15)(p11.2;p13) and der(9;21)t(9;21)(p13.1;p13.1). One patient presented two concomitant rearranged chromosomes: a der(12)t(9;12)(q21.13;p13.33) and an psu i(9)(p10) which showed FISH centromeric signal smaller than in the normal chromosome 9. Besides the duplication 9p24.3p13.1, array revealed a 7.3 Mb deletion in 9q13q21.13 in this patient. The break in the psu i(9)(p10) probably occurred in the centromere resulting in a smaller centromere and with part of the 9q translocated to the distal 12p with the deletion 9q occurring during this rearrangement. Two patients, brother and sister, present 9p duplication concomitant to 18p deletion due to an inherited der(18)t(9;18)(p11.2;p11.31)mat. The patients with trisomy 9p present a well-recognizable phenotype due to facial appearance, although the genotype-phenotype correlation can be difficult due to concomitant partial monosomy of other chromosomes. The chromosome 9 is rich in segmental duplication, especially in pericentromeric region, with high degree of sequence identity to sequences in 15p, 18p and 21p, chromosomes involved in our rearrangements. Thus, we suggest that chromosome 9 is prone to illegitimate recombination, either intrachromosomal or interchromosomal, which predisposes it to rearrangements, frequently involving pericentromeric regions.

Introduction: Ring chromosome 15 is a rare disorder, with only a few over 40 cases reported in the literature. There are only two previous reports of cases where patients with ring chromosome 15 have been followed-up. Case presentation: We report here on the 20-year clinical and cytogenetic follow-up of a patient with a ring chromosome 15. Our patient, a Caucasoid Asian woman, presented with short stature, microcephaly, minor dysmorphic features, hyperextensible knees, generalized hirsutism, café-au-lait and small hypochromic spots spread over her face and the front of her chest and abdomen, dorsolumbar scoliosis and mild intellectual disability. She was followed-up from the age of eight to 28 years. When she was 27 years old, she was reported by her mother to present with compulsive overeating and an aggressive mood when challenged. Karyotyping revealed that the majority of her cells harbored one normal chromosome and one ring chromosome. Silver staining revealed the presence of the nucleolar organizer region in the ring chromosome. Ring loss and/or secondary aberrations exhibited a slight increase over time, from 4.67% in 1989 to 7.67% in 2009, with the presence of two monocentric rings, cells with interlocked rings, a dicentric ring, and broken or open rings. A genome-wide array technique detected a 5.5Mb deletion in 15q26.2. Conclusions: We observed that some phenotypic alterations in our patient can be associated with gene loss and haploinsufficiency. Other features may be related to different factors, including ring instability and epigenetic factors.

Background: The majority of Marfan syndrome (MFS) cases is caused by mutations in the fibrillin-1 gene (FBN1), mapped to chromosome 15q21.1. Only few reports on deletions including the wholeFBN1gene, detected by molecular cytogenetic techniques, were found in literature.Results: We report here on a female patient with clinical symptoms of the MFS spectrum plus craniostenosis, hypothyroidism and intellectual deficiency who presents a 1.9 Mb deletion, including theFBN1gene and a complex rearrangement with eight breakpoints involving chromosomes 6, 12 and 15.Discussion: This is the first report of MFS with a complex chromosome rearrangement involving a deletion ofFBN1and contiguous genes. In addition to the typical clinical findings of the Marfan syndrome due toFBN1gene haploinsufficiency, the patient presents features which may be due to the other gene deletions and possibly to the complex chromosome rearrangement.

The breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients.