Allelic frequencies and statistical data obtained from 12 codis STR loci in an admixed population of the Brazilian Amazon

The allelic frequencies of 12 short tandem repeat loci were obtained from a sample of 307 unrelated individuals living in Macapá, a city in the northern Amazon region, Brazil. These loci are the most commonly used in forensics and paternity testing. Based on the allele frequency obtained for the population of Macapá, we estimated an interethnic admixture for the three parental groups (European, Native American and African) of, respectively, 46 percent, 35 percent and 19 percent. Comparing these allele frequencies with those of other Brazilian populations and of the Iberian Peninsula population, no significant distances were observed. The interpopulation genetic distances (F ST coefficients) to the present database ranged from F ST = 0.0016 between Macapá and Belém to F ST = 0.0036 between Macapá and the Iberian Peninsula.

Mutational and Loss of Heterozygosity Analysis of the p53 and PTEN Tumor Suppressor Genes in Breast Carcinoma

BACKGROUND: Although the genetic determinants of most sporadic breast cancers remain unknown, the understanding of the molecular and genetic events that contribute to breast carcinogenesis has been significantly advanced. We investigated the clinicopathologic significance of allelic imbalance or mutation of both p53 and PTEN tumor suppressor genes in sporadic breast carcinomas. METHODS: Genomic DNA from 62 breast carcinoma cases was extracted from paraffin blocks, and PCR was performed to determine loss of heterozygosity (LOH) for DNA markers around the p53 and PTEN genes and to amplify exons 5, 6, 7, and 8 of p53 and all 9 coding axons of PTEN. RESULTS: Somatic p53 mutations were detected in 6 (9.7%) of the 62 cases. LOH for DNA markers surrounding p53 was observed in 18 (29.0%) of the 62 cases. LOH for DNA markers surrounding PTEN was detected in 29 (46.8%) of the 62 cases. Only one case (1.6%) showed somatic PTEN mutations. Tumors with LOH on 17p or p53 mutation were large in size and negative for ER, had a high Ki-67 index, and exhibited p53 immunoreactivity (p<0.05). Tumors with LOH on 10q23 were associated with c-erbB-2 positivity (p=0.018). CONCLUSIONS: Our results indicate that LOH at 17p and/or p53 mutation is significantly associated with the aggressive pathologic parameters of breast cancer.

Inactivación del gen CDKN2A (p16) en cáncer de la vesícula biliar / Inactivation of CDKN2A gene (p16) in gallbladder carcinoma

Background: The CDKN2A gene encodes a cyclin dependent kinase inhibitor, p16, which promotes cell cycle arrest. Methylation of the promoter region trans-criptionally inactivates the gene. Aim: To study the relationship between methylation status of the prometer region of p16 gene, the immunohistochemical expression of p16 and clinical and morphological features of gallbladder carcinoma. Material and methods: We analyzed the methylation status of the promoter region of the CDKN2A gene in gallbladder adenocarcinomas using methylation specific PCR (MSP). We also used microsatellite markers near the CDKN2A gene to detect allelic imbalance (AI) and examined the tumors by immunohistochemistry (IHC) for p16 expression. Results: Of 38 gallbladder adenocarcinomas analyzed by IHC, 11 cases (29%) were negative for p16 protein. Nine (24%) had methylation of the promoter region of the CDKN2A gene. Twenty nine cases were negative for methylation, but four (14%) of these 29 exhibited AI at one or more of the microsatellite markers. CDKN2A promoter methylation was not associated with microsatellite instability (MSI-H). Conclusions: The inactivation of CDKN2A by methylation and/or deletion might play an important role in gallbladder carcinogenesis.

Allelic imbalance studies of chromosome 9 suggest major differences in chromosomal instability among nonmelanoma skin carcinomas

CONTEXTO: Vários estudos de perda de heterozigozidade na região 9p21-p22, que abriga os genes supressores tumorais CDKN2a/p16INK4a, p19ARF e p15INK4b, têm sido realizados em uma ampla série de tumores humanos, incluindo os melanomas familiares. Perdas e ganhos em outras regiões do cromossomo 9 também têm sido observados com freqüência e podem indicar mecanismos adicionais no processo de tumorigênese dos carcinomas basocelulares da pele. OBJETIVO: Investigar o equilíbrio alélico existente na região 9p21-p22 em carcinomas basocelulares. TIPO DE ESTUDO: Análise molecular de marcadores de microssatélites em tumores e controles. LOCAL: Dois serviços de dermatologia de atendimento terciário em universidades públicas de São Paulo e o Laboratório de Genética Molecular do Câncer da Universidade Estadual de Campinas (Unicamp), Brasil. PARTICIPANTES: Examinamos 13 casos benignos, incluindo 4 queratoses solares, 3 queratoacantomas, 3 nevos melanocíticos, 2 doenças de Bowen e 1 neurofibroma cutâneo, além de 58 tumores malignos da pele: 14 de células escamosas, 40 carcinomas basocelulares e 4 melanomas; em pacientes consecutivamente encaminhados à clínica de Dermatologia da Unicamp e que concordaram em participar do estudo. VARIÁVEIS ESTUDADAS: O tumor principal e uma porção normal de pele não-adjacente foram removidos cirurgicamente de pacientes que consecutivamente procuraram os ambulatórios de dermatologia da Universidade Estadual de Campinas (Unicamp) e da Universidade Estadual de São Paulo (Unesp), São Paulo, por causa de lesões cutâneas. Extraímos DNA tanto de tecido tumoral como do correspondente tecido normal de cada paciente. Para amplificar regiões de repetição polimórfica de microssatélites do cromossomo 9, foram utilizados quatro pares de primers, sendo dois deles destinados à região 9p21-p22. RESULTADOS: Identificamos oito casos (20%) de desequilíbrio alélico entre os carcinomas basocelulares, sendo dois casos de perda de heterozigozidade e seis casos de instabilidade de microssatélite na região 9p21-p22. Outros marcadores também mostravam anormalidades em três destes tumores, enquanto nenhuma alteração foi detectada entre os casos benignos e nos outros tumores malignos. CONCLUSÃO: Esta dependência fenotípica sugere que existem diferenças importantes no comportamento das formas mais comuns de tumores cutâneos não-melanocíticos em relação à sua tendência para instabilidade de microssatélite no cromossomo 9...

Genome-wide genetic study of medulloblastoma using allelotype analysis / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate global genetic alterations in medulloblastoma, and to localize critical chromosomal loci with allelic imbalances associated with the development of medulloblastoma.</p><p><b>METHODS</b>A high-resolution genome-wide allelotype analysis, including 384 microsatellite markers, was performed in 12 medulloblastomas.</p><p><b>RESULTS</b>An average of 238 (62.3%) allelic imbalances were detected on all 39 autosomal arms. Non-random allelic gains or losses were detected on chromosomes 7q (58.3%), 8p (66.7%), 16q (58.3%), 17p (58.3%) and 17q (66.7%). In addition, chromosomal arms with frequencies of allelic imbalances higher than the mean percentage were identified on 3p (33.3%), 3q (33.3%), 4q (41.7%), 7p (33.3%), 8q (41.7%), 10q (41.7%), 13q (33.3%), 14q (33.3%) and 20q (33.3%). No relationship was found between the frequency of allelic imbalances and the clinical outcome of the patients.</p><p><b>CONCLUSIONS</b>A global view of the genetic alterations in medulloblastoma was provided. The allelic imbalances involving chromosomes 7q, 8p, 16q, 17p and 17q may play an important role in the pathogenesis of medulloblastoma.</p>

Relationship between microsatellite alterations on chromosome 8 and clinicopathological characteristics in hepatocellular carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the features of microsatellite alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Ten high-polymorphic microsatellite markers on chromosome 8 were selected to detect the loss of heterozygosity (LOH), microsatellite instability (MSI) and allelic imbalance (AI) in 56 HCCs using automatic capillary array electrophoresis DNA analysis system.</p><p><b>RESULTS</b>LOH was found in 37 of 56 HCCs (66.1%) on at least 10 locus. The three most frequently altered loci were D8S261 (53.5%, 23/43), D8S1721 (52.5%, 21/40) and D8S1771 (52.5%, 21/40). LOH on D8S277 was significantly higher in cases with positive serum HBsAg than in those with negative HBsAg (P < 0.01). Similarly, LOH on D8S261, D8S298 and D8S1733 occurred more frequently in patients with negative HBsAg than those with positive HBsAg (P < 0.01). LOH on D8S298 and D8S1771 were more frequent in tumors larger than 3 cm in size (P < 0.05 and P < 0.01 respectively). LOH frequencies of D8S1721 were significantly higher in cases with absent or partially encapsulated tumor than in those with intact tumor capsule (P < 0.05). LOH on D8S298 and D8S1771 were more frequently detected in tumors with intrahepatic metastasis than those without (P < 0.01). MSI was found in 12.5% (7/56) cases. AI was found in 19.6% (11/56) of all cases examined.</p><p><b>CONCLUSIONS</b>Microsatellite alterations on chromosome 8 were frequent in HCC. LOH, possibly representing alterations of the tumor suppressor pathway, may play an important role in hepatocarcinogenesis. MSI, reflecting a dysfunction of the mismatch repair pathway, may also contribute to this process, but in a less significant way. LOH at some particular loci is associated with certain clinicopathological parameters of human HCC.</p>

A Study on the Loss of Heterozygosity of the p53 Gene in Primary Uterine Cervical Carcinomas / 대한암학회지

PURPOSE: Allelic deletion of p53 tumor suppressor gene have been observed frequently in a variety of human tumors. These losses are believed to contribute to the development of human cancers. But the loss of heterozygosity (LOH) data on chromosome 17p are rare and controversial with respect to cervical carcinomas. So, we tried to elucidate the frequency of p53 locus LOH in primary cervical carcinoma and compared the LOH data with clinicopathological parameters. MATERIALS AND METHODS: In order to detect LOH within one of the well-known tumor suppressor gene, p53, three intragenic polymorphisms (exon 1, exon 4, and intron 6) and one microsatellite distal to the p53 gene (D17S5) were examined. Paired DNA samples from 55 primary uterine cervical carcinomas and normal bloods were studied for the chromosomal allelic loss of p53 gene locus by polymerase chain reaction (PCR), the presence of human papilloma virus (HPV), and the presence of p53 gene point mutation by PCR-single conformation polymorphism (SSCP) analysis. And the relationships between allelic losses of this gene and conventional clinicopathological parameters were evaluated. RESULTS: We could increase the heterozygosity of the p53 gene up to 1 (100%). The observed allelic loss rate of the p53 locus in informative cases was 5.5% (3/55) and the observed allelic loss rate of the D17S5 locus in informative cases was 8.7% (4/46) . Only one of the four patients with LOH at the D17S5 locus showed a concomittant allelic loss of the p53 gene. The overall LOH incidence of the chromosomal region comprising 17p13.1 (p53) to 17p13.3 (D13S5) was 10.9% (6/55). All the samples contained at least one of the oncogenic HPV type 16 and/or 18 sequences. No shifted bands were observed in the PCR-SSCP analysis of the p53 gene. The LOH of the p53 gene was not related to other parameters including clinical stage, histological type, and degree of differentiation. CONCLUSION: Concerning with the results above, we conclude that the allelic imbalance of the p53 gene itself is not implicated as a major contributing factor in the malignant transformation or the tumor progression in HPV-positive cervical cancers. Another putative tumor suppressor gene which has more important function than p53 gene in cervical carcinogenesis might exist between these two loci [p53 (17p13.1) and D17S5 (17p13.3)].