Seroconversion panels demonstrate anti-SARS-CoV-2 antibody development after administration of the mRNA-1273 vaccine.

Seroconversion panels are an important tool for investigating antibody responses in acute and chronic phases of disease and development of serological assays for viral diseases including COVID-19. Globally it is anticipated that vaccines against SARS-CoV-2 will facilitate control of the current pandemic. The two COVID-19 seroconversion panels analyzed in this study were obtained from healthcare workers with samples collected before vaccination with the mRNA-1273 vaccine (Moderna) and after the first and second doses of the vaccine. Panel samples were tested for antibodies to SARS-CoV-2 (IgG). Individual subjects with a positive response for anti-SARS-CoV2 IgG in their pre-vaccination samples showed a significantly enhanced response to the first vaccination. In older subjects, lower immunological responses to the first injection were observed, which were overcome by the second injection. All subjects in the study were positive for anti-SARS-CoV-2 IgG after the second dose of vaccine.

Available COVID-19 serial seroconversion panel for validation of SARS-CoV-2 antibody assays.

Seroconversion panels are an important tool for investigating antibody responses and developing serological assays. A seroconversion panel was generated from a single SARS-CoV-2 positive plasma donor over 87 days. This seroconversion panel was tested against 6 SARS-CoV-2 antibody tests (IgG, IgM, and total Ig). All test kits utilized recombinant antigens that are specific to SARS-CoV-2. The seroconversion panel showed IgG responses for SARS-CoV-2 after day 50. IgM levels peaked on day 50 (prior to IgG) and declined in subsequent samples. This seroconversion panel is a useful tool for validation of SARS-CoV-2 antibody assays.

Nasopalpebral lipoma-coloboma syndrome: clinical, radiological, and histopathological description of a novel sporadic case.

Nasopalpebral lipoma-coloboma syndrome is an extremely uncommon autosomal dominant condition characterized by congenital upper eyelid and nasopalpebral lipomas, colobomata of upper and lower eyelids, telecanthus, and maxillary hypoplasia. A few familial and sporadic cases of this malformation syndrome have been previously reported. Here, the clinical, radiological, and histopathological features of a sporadic Mexican patient with the nasopalpebral lipoma-coloboma syndrome are described. To our knowledge, this is the first time that craniofacial 3D computed tomography imaging was used for a detailed assessment of the facial lipoma.

Mucopolysaccharidosis type II in a female carrying a heterozygous stop mutation of the iduronate-2-sulfatase gene and showing a skewed X chromosome inactivation.

We report a Mexican girl showing the full blown clinical picture of mucopolysaccharidosis type II (MPSII). Iduronate-2-sulfatase (IDS) activity was low and she carried a heterozygous de novo c.1327C>T transition in exon 9, that changes codon 443 for a premature stop (TGA; p.Arg443(*)). Analysis of X-chromosome inactivation in androgen receptor (AR) locus showed a highly skewed ratio of 92:8 suggesting a functional hemizygosity with dominant expression of the mutant IDS and explaining the disease manifestation. This is one of the rare cases of females affected by MPSII due to the combined effect of a skewed X-chromosome inactivation and a de novo IDS mutation. We recommend that clinicians should consider the diagnosis of MPSII even in a girl without positive family history for this condition.

P14ARF gene alterations in human hepatocellular carcinoma.

INTRODUCTION: The molecular status of the p14(ARF) gene has not been fully elucidated in hepatocellular carcinoma (HCC). This study was performed to determine genetic and epigenetic alterations in the p14(ARF) tumor suppressor gene and their effect on HCC progression. METHODS: The status of p14 was evaluated in 117 HCC tumoral nodules and 110 corresponding non-tumor tissues by loss of heterozygosity at the 9p21-22 region, homozygous deletions, single strand conformation polymorphism-polymerase chain reaction mutational analysis and methylation-specific polymerase chain reaction. RESULTS: The most frequent inactivation mechanism was hypermethylation of the promoter region, which was found in 41.9% of tumor samples and in 19.1% of non-tumor samples. Loss of heterozygosity at the 9p21 region was detected in 27.3% and 10% of tumor and non-tumor tissues, respectively. Homozygous deletions and mutations were less common events in hepatocarcinogenesis. We found 5.9% of the tumor cases with exon 2 homozygous deletions and 3.4% of the cases with mutations. We described a silent mutation in codon 42 of exon 1beta for the first time. No association was found between inactivation of p14(ARF) and clinicopathological characteristics or prognosis. CONCLUSION: We can conclude that p14(ARF) is frequently and early altered in HCC, being the main cause of inactivation promoter hypermethylation. Our results suggest that the p14(ARF) gene plays an important role in the pathogenesis of hepatocellular carcinoma.

p16INK4A gene alterations are not a prognostic indicator for survival in patients with hepatocellular carcinoma undergoing curative hepatectomy.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a common malignancy worldwide that is highly associated with chronic hepatitis B or C infection and cirrhosis. The tumor suppressor gene p16INK4A is an important component of the cell cycle and inactivation of the gene has been found in a variety of human cancers. The present study was performed to determine genetic and epigenetic alterations in the p16INK4A tumor suppressor gene and the effect of these on HCC progression. METHODS: The status of p16INK4A was evaluated in 117 HCC tumoral nodules and 110 corresponding peritumoral tissues by loss of heterozigosity (LOH) at the 9p21-22 region, homozygous deletions, single-strand conformation polymorphism-polymerase chain reaction (PCR) mutational analysis and methylation specific PCR. RESULTS: The most frequent inactivation mechanism was hypermethylation of the promoter region, which was found in 63.2% of the tumor samples and in 28.2% of the peritumoral samples. Loss of heterozygosity at the 9p21 region was detected in 27.3% and 10% of tumor and peritumoral tissues, respectively. Homozygous deletions and mutations were less common events in hepatocarcinogenesis. The authors found 5.9% of the tumor cases with exon 2 homozygous deletions and 8.6% with mutations. Two polymorphisms were detected, one at codon 148 (GCG --> ACG, Ala --> Thr) in three cases and the other in exon 3 at 540 bp (34.2% of the samples). No association was found between inactivation of p16INK4A and clinicopathological characteristics or prognosis. CONCLUSION: p16INK4A is altered frequently and early in HCC, being the predominant mechanism of inactivation promoter hypermethylation. The present results suggest that the p16INK4A gene plays an important role in the pathogenesis of HCC.

No association between GSTP1 gene aberrant promoter methylation and prognosis in surgically resected hepatocellular carcinoma patients from the Basque Country (Northern Spain).

AIMS: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, being linked etiologically to several factors. Glutathione-S-transferases (GSTs) are a family of enzymes that play an important role in detoxification. Hypermethylation of regulatory sequences at glutathione-S-transferase pi class gene (GSTP1) has been found in different human tumor types. In this study, we have studied the methylation status of the GSTP1 promoter region in patients from the Basque Country (Northern Spain) by methylation-specific PCR (MSP). METHODS AND RESULTS: GSTP1 aberrant promoter methylation was present in 24 of 117 (20.5%) tumor samples being associated with late stages of tumor progression. Patients with multiple HCCs showed different patterns of methylation, which could suggest a different clonal origin of multicentric HCC or different degrees of differentiation. No effect on disease-free survival or overall survival was observed in patients with GSTP1 methylated who underwent curative resection. CONCLUSIONS: We can conclude that GSTP1 promoter CpG island methylation appears to be a less common event during hepatocarcinogenesis in European populations than in Asian populations, being associated with late stages of tumor progression. These findings could also be useful to provide new therapeutic strategies through the use of demethylating agents.

Frequent loss of p53 codon 72 Pro variant in hepatitis C virus-positive carriers with hepatocellular carcinoma.

Codon 72 exon 4 polymorphism of the p53 gene has been implicated in cancer risk and it has been suggested that it may have an impact on the clinical outcome of the disease. Our objective was to evaluate the association between p53 polymorphism at codon 72 and hepatocellular carcinoma. The p53 codon 72 genotype was examined in 97 biopsy samples from 67 Basque patients histologically diagnosed with hepatocellular carcinoma. Blood samples collected from 111 Basque residents were examined as a control group. The polymorphism was examined by both single strand conformation polymorphism analysis and allele specific polymerase chain reaction. Fisher's exact test was used to evaluate the data. The results showed that there were no statistically significant differences in the frequency of codon 72 polymorphism genotype between patients with liver cancer and healthy controls. We found a frequent loss of proline allele in hepatitis C virus (HCV)-positive carriers. In conclusion, the lack of a significant relationship between this polymorphism and risk of hepatocellular carcinoma suggests that it does not predispose towards hepatocarcinogenesis in this population. We suggest that the frequent loss of the proline allele in HCV-associated carcinogenesis of the liver plays some role in hepatocarcinogenesis.