Jorge García Martínez

Wood dust–related mutational profile of TP53 in intestinal-type sinonasal adenocarcinoma

Intestinal-type sinonasal adenocarcinoma represents 8% to 25% of all malignant sinonasal cancer and is etiologically related to occupational exposure to wood dust. Despite its clear etiology, the mechanisms behind the carcinogenic effects of wood dust are unclear. Because it is known that carcinogens can leave specific mutational fingerprints, we aimed to analyze the spectrum of TP53 mutations and to relate the findings to the wood dust etiology of the patients. Forty-four primary tumors were examined for TP53 mutations by direct sequencing. In addition, p53 protein expression was analyzed by immunohistochemistry using a tissue microarray consisting of 92 tumors. We report a frequency of 41% (18/44) TP53 mutations and 72% (66/92) p53 immunopositivity in intestinal-type sinonasal adenocarcinoma, significantly related to wood dust, but not to tobacco etiology. G→A transition (50%, 9/18 cases) was the most common alteration detected, almost exclusively found in nonsmokers, whereas G→T (27%, 5/18 cases) was detected in smokers only. These data point to wood dust exposure as the causal factor in the mutagenesis of TP53, possibly caused by reactive nitrogen species generated through a chronic inflammatory process.

Microsatellite instability analysis of sinonasal carcinomas

OBJECTIVES: Intestinal-type sinonasal adenocarcinoma (ITAC) and squamous cell carcinoma of the nasal cavity (SCCNC) are histopathologically but not etiologically similar to colorectal adenocarcinoma or to laryngeal squamous cell carcinoma, respectively. Microsatellite instability (MSI) is involved in both tumors. The aim of this study was to investigate a possible role for MSI in the pathogenesis of two types of nasal carcinoma. MATERIAL AND METHODS: DNA obtained from frozen tumor samples of 41 ITACs and 24 SCCNCs was analyzed for shifts in five mononucleotide microsatellite loci by multiplex PCR. RESULTS: The allelic patterns of one ITAC (2%) and five SCCNCs (21%) revealed an allelic shift for at least one of the five loci, indicating microsatellite instability. CONCLUSION: MSI may be involved in squamous cell carcinoma, but not in adenocarcinoma of the nasal cavities.

Localization of centromeric breaks in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) have very complex karyotypes that show all types of structural rearrangements. The most frequent aberrations are whole-arm translocations, which appear to have their breakpoints in centromeric or pericentromeric regions. We aimed to pinpoint the exact location of the breakpoints of these marker chromosomes with high-resolution cytogenetic and genetic analyses using microarray comparative genomic hybridization (CGH), multiplex ligation-dependent probe amplification (MLPA), and fiber fluorescence in situ hybridization (FISH). Among the seven cell lines in this study, six (84%) harbored one or more centromeric breakpoints or whole-arm translocations. In total, microarray CGH identified 163 breakpoints, 47 (29%) of which were in centromeric regions. Microarray CGH and MLPA results indicated that the translocation breakpoints were localized between the microarray oligonucleotide clones and MLPA probes closest to the centromere. High-resolution fiber-FISH revealed adjacent or minimally overlapping signals of probes that recognize the pericentromeric sequences of the two participating chromosomes. This indicates that whole chromosome arm translocation breakpoints occur within the pericentromeric chromatin and not the centromere core sequences.

Las infecciones por virus herpes simplex, Epstein-Barr, varicela zoster, papiloma humano, citomegalovirus o adenovirus no tienen relación con los adenocarcinomas nasosinusales☆

Objetivo Se ha relacionado a diversos virus con el desarrollo de tumores epidermoides de cabeza y cuello. No obstante, no existen estudios previos que relacionen a los adenocarcinomas nasosinusales (ACN) con la presencia de virus. El objetivo de este estudio es determinar, en una serie de ACN, la presencia de virus que se sabe desempenan un papel en el cancer. Material y metodo Se estudio mediante PCR 37 ACN, para determinar la presencia de ADN de virus de papiloma humano, virus de Epstein-Barr (VEB), virus herpes simplex, virus de la varicela zoster, adenovirus y citomegalovirus. Resultados Se detecto ADN de VEB en 3 (8,1 %) de las 37 muestras tumorales y ADN de citomegalovirus en 1 (2,7 %) de los 37 casos analizados. Conclusiones Nuestros resultados indican que los virus estudiados no desempenan papel alguno en la etiologia de los ACN.

Medullary thyroid carcinoma and 2q37 deletion in a patient with nevoid basal cell carcinoma syndrome: Clinical description and genetic analysis

Nevoid basal cell carcinoma syndrome (NBCCS) is a rare, inheritable, multisystem disorder characterized by numerous basal cell carcinomas (BCCs), maxillary keratocyst, and musculoskeletal malformations. Occasionally, it is associated with malignancies like rhabdomyoma, melanoma, and sinonasal undifferentiated carcinoma, to name a few.

Viral Infection of Herpes simplex, Epstein-Barr, Varicela Zoster, Human Papilloma, Cytomegalovirus, or Adenovirus Are Not Related to Sinonasal Adenocarcinomas

OBJECTIVE Several types of virus have been implicated in the development of head and neck tumors. However, until now sinonasal adenocarcinomas (ACN) have not been studied. The aim of this study is to screen a series of ACN for the presence of a number of viruses known to play a role in cancer. MATERIAL AND METHOD Viral DNA sequences of herpes simplex virus, Epstein-Barr, varicela zoster, human papilloma, cytomegalovirus, and adenovirus were analysed by PCR in 37 primary ACN. RESULTS Three tumors (8.1%) were positive for Epstein-Barr virus and 1 case (2.7%) for cytomegalovirus. CONCLUSIONS Viral infections do not seem to play a role in the etiology of ACN.

DNA aneuploidy‐specific therapy for head and neck squamous cell carcinoma

Patients with head and neck squamous cell carcinoma (HNSCC) have an unfavorable prognosis, with a 5‐year survival rate of approximately 40%. Genetic analyses have revealed that the majority of HNSCCs carry complex, aneuploid karyotypes, showing numerical and structural chromosomal imbalances. New compounds are being developed that target chromosomal instability in general, specifically affecting cells with aneuploid karyotypes.

Fe de errores de Análisis de la inestabilidad de microsatélites en el carcinoma escamoso de laringe

Introduction and objectives: The literature on the involvement of microsatellite instability in head and neck squamous cell carcinoma shows great variability, probably due to differences in the testing methods. Using a consensus detection system, we aimed to reach a reliable estimate of microsatellite instability prevalence in a subset of head and neck squamous cell carcinoma

Análisis de la inestabilidad de microsatélites en el carcinoma escamoso de laringe

INTRODUCTION AND OBJECTIVES The literature on the involvement of microsatellite instability in head and neck squamous cell carcinoma shows great variability, probably due to differences in the testing methods. Using a consensus detection system, we aimed to reach a reliable estimate of microsatellite instability prevalence in a subset of head and neck squamous cell carcinoma cases. METHODS The microsatellite instabilityI status of 43 patients with previously untreated primary laryngeal squamous cell carcinomas was analyzed by a multiplex polymerase chain reaction assay including 5 mononucleotide repeat markers. RESULTS Thirty-six cases showed a stable phenotype or a microsatellite stable phenotype (83.7%) and 7 cases (16.3%) showed an microsatellite instability-positive phenotype. One case showed instability in 3 of 5 markers, 1 case in 2 markers and 5 cases in 1 marker. The microsatellite instability-positive and stable cases did not differ with respect to age, tumour stage, lymph node or distant metastases. CONCLUSIONS Our data showed that a proportion of laryngeal squamous cell carcinomas are microsatellite instability positive. Knowledge of microsatellite instability patient status will allow adjusting anticancer therapy at an individual level.