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The biallelic inheritance of an expanded intronic pentamer (AAGGG)A retrospective descriptive study from an ataxia database comprising 500 patients.The study was performed at the Otorhinolaryngology Department of a hospital in the north of Spain.Specific genetic testing for CANVAS was performed in 13 patients with clinical suspicion of complete or incomplete syndrome. The clinical diagnosis was supported by quantitative vestibular hypofunction, cerebellar atrophy, and abnormal sensory nerve conduction testing.Nine of 13 (69%) patients met clinical diagnostic criteria for definite CANVAS disease. The first manifestation of the syndrome was lower limb dysesthesia in 8 of 13 patients and gait imbalance in 5 of 13. Eleven of 13 (85%) patients were carriers of the biallelic (AAGGG)A genetic cause of CANVAS has recently been discovered. We propose genetic screening for biallelic expansions of the AAGGG pentamer of

To identify epigenetic events in intestinal-type sinonasal adenocarcinoma (ITAC) and sinonasal squamous cell carcinoma (SNSCC) and to evaluate their relation to clinicopathologic features and follow-up data.Retrospective study.Academic research hospital.The methylation status of 23 genes in 50 ITACs and 32 SNSCCs was analyzed by methylation-specific multiplex ligation-dependent probe amplification and its relation to clinicopathologic features and follow-up data.Gene methylation was observed in 50% of all tumors. Recurrent methylated genes in SNSCC were RASSF1 and CDH13 (for both, 6 of 32 cases), CHFR (4 of 32 cases), and TIMP3 (2 of 32 cases). None of these genes showed significant correlation to clinicopathologic features or overall survival. In ITAC, recurrent methylated genes were CDH13 (18 of 50 cases), ESR1 (13 of 50 cases), APC (7 of 50 cases), TIMP3 (5 of 50 cases), CASP8 (3 of 50 cases), and HIC1 and RASSF1 (for both, 2 of 50 cases). Papillary and colonic ITAC subtypes carried a mean of 1.26 gene methylations per tumor versus 0.63 in solid and mucinous subtypes. Methylation of TIMP3 was associated with a significantly worse survival in ITAC patients.ITAC carries a higher number and a different profile of gene methylations as compared with SNSCC. Gene methylation plays a greater role in papillary and colonic ITAC subtypes, which may indicate a different tumorigenic pathway for these ITAC subtypes. These findings could be used as prognosticators and may have implications for future individualized therapies based on epigenetic changes.

Objective Paragangliomas (PGLs) of the head and neck are benign neoplasms derived from the autonomic nervous system. Familial PGLs have been associated with germline mutations in succinate dehydrogenase (SDH) genes, and occasionally in Von Hippel–Lindau (VHL) and RET. The aim of this study was to compare somatic DNA copy number changes in tumors of familial and sporadic origin. Material and Methods Eight familial and 16 sporadic patients were analyzed for germline mutations and exon deletions in SDHB, SDHC, SDHD, VHL, and RET by direct sequencing and MLPA. Microarray CGH analysis was applied to map genome-wide somatic copy number changes. Results Fifteen cases carried a germline mutation in SDHB or SDHD, four of which not described before. Microarray CGH detected abnormalities in 10 of 18 cases, most frequently concerning deletions at 1p, 1q, and 11q, the sites where SDH are located. However, these deletions occurred in both SDH mutation–positive and SDH mutation–negative cases. Conclusions These data suggest that inactivating germline SDH mutations and somatic deletions of SDH genes as a “second hit” are involved in a subset, but not in all PGLs. Additional genes and mechanisms may need to be studied, especially in the group of sporadic PGL showing no chromosomal aberrations.

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.

OBJECTIVE: Assess the amplification of CCND1, EMS1, PIK3CA, ERBB1, and ERBB2 oncogenes in ethmoid sinus adenocarcinomas.STUDY DESIGN AND SETTING: Tissue samples from 13 primary ethmoid adenocarcinomas and 2 recurrences were studied at Hospital Central de Asturias, Oviedo, Spain, between July 1998 and February 2002. A semiquantitative evaluation of CCND1, EMS1, PIK3CA, ERBB1, and ERBB2 amplification was performed by multiplex polymerase chain reaction.RESULTS: Three (23%) cases presented CCND1 amplification, one of them with a concurrent PIK3CA amplification. EMS1 was amplified in the 2 studied recurrences. ERBB1 was amplified in 1 case (8%), whereas none presented ERBB2 amplification. Oncogenic amplifications were only detected in advanced (stage III) tumors; however, no prognostic value could be shown for them.CONCLUSIONS: CCND1, EMS1, PIK3CA, and ERBB1 amplifications are uncommon and appear to be late events in the development of ethmoid sinus adenocarcinoma.SIGNIFICANCE: New information on the carcinog...

ObjectivesIntestinal-type adenocarcinomas of the nasal cavity (ITAC) are histopathologically similar to colorectal adenocarcinoma. Professional exposure to wood dust is a strong etiological factor, although the mechanism is not understood. Little is known about the genetic changes in sinonasal adenocarcinomas. Our goals were: 1) Identify genome-wide recurrent DNA copy number changes, and 2) Evaluate their relation to clinico-pathological characteristics.Methods44 ITAC, 36 of wich related to professional exposure to wood dust, were studied by microarray CGH analysis using a 30,000 oligonucleotide set. In addition, MLPA was applied to identify copy number changes of 60 different tumor-related genes.ResultsThe most frequent chromosome gains were, in descending order: 5p15,20q13, 8q24, 20q11 and 8q21. Losses occurred most frequently at: 4q31-qter, 18q12-22, 8p12-pter, 5q11-qter, 10q22-23 and 17p13. Recurrent high level amplifications were detected at 7p11, 8p11 and 8q24. MLPA confirmed the overall pattern of ...

Polymerase chain reaction (PCR) has provided new insights in molecular biology. Recently, some studies have been focused on temporal bone pathology, with amplification of DNA from fixed sections of celloidin-embedded bones. The purpose of our study was to elucidate the utility of PCR in detection of minor concentrations of DNA from nonoptimal stored samples. We obtained geniculate ganglia from 30 temporal bones preserved in formalin for a long time, without any process of embedding. By performing a nested PCR assay, we detected herpes simplex virus type 1 DNA in 13 of 30 ganglia (43%). We conclude therefore that study of temporal bones stored under poor conditions by PCR is possible, although there are some limitations when compared with fresh or optimally archived samples. (Otolaryngol Head Neck Surg 2000;123:508-11.)

A retrospective review of 302 previously untreated patients with primary supraglottic carcinoma was undertaken to ascertain the efficacy of postoperative radiotherapy. The 302 patients underwent a total of 383 functional neck dissections and 45 classic radical neck dissections. Pathological examination revealed nodal involvement in 117 patients (39%). In the histologically N0 group, the incidence of contralateral neck recurrence when a unilateral neck dissection and postoperative radiotherapy were carried out was 8%, rising 21% when no postoperative radiation was given. There was no difference in the ipsilateral recurrence rate in the N0 group, radiated patients (3%) and nonradiated patients (2%). Similar figures were found in the N1 group. Bilateral functional neck dissection in histologically N0, N1, and N2 necks had similar recurrence rates with or without radiotherapy. Distant metastasis appeared in 10% of N0 patients and in 35% of N3 patients. Patients who received postoperative radiotherapy showed a significantly higher rate of distant metastasis (21%) than patients who did not (8%). The number of involved lymph nodes had no relevance both in neck recurrence and distant metastasis.

Objectives1) To present the objective and subjective analysis of voice quality following treatment of an early epidermoid glottic carcinoma. 2) Results from the objective evaluation of the voice, along with the self-evaluation of voice quality quantified using the Voice Handicap Index of a group of patients treated with endoscopic laser surgery, are compared with patients treated with radiotherapy.MethodsWe performed an objective voice evaluation, as well as a physical, emotional, and functional well-being assessment of 19 patients treated with laser surgery and 18 patients treated with radiotherapy. The data obtained was gathered in the statistical database SPSS 12.0. The statistical analysis used was the “Student t test” in order to compare averages and the Chi-squared test for comparing proportions. The statistical differences were considered significant when p was lower than 0.05.ResultsVoice quality is affected both by surgery and radiotherapy. Voice parameters only show differences in the maximum ph...