Rare copy number alterations and copy-neutral loss of heterozygosity revealed in ameloblastomas by high-density whole-genome microarray analysis.

BACKGROUND: Ameloblastoma (unicystic, UA, or multicystic, MA) is a rare tumor associated with bone destruction and facial deformity. Its malignant counterpart is the ameloblastic carcinoma (AC). The BRAFV600E mutation is highly prevalent in all these tumors subtypes and cannot account for their different clinical behaviors. METHODS: We assessed copy number alterations (CNAs) and copy-neutral loss of heterozygosity (cnLOH) in UA (n = 2), MA (n = 3), and AC (n = 1) using the CytoScan HD Array (Affymetrix) and the BRAFV600E status. RT-qPCR was applied in four selected genes (B4GALT1, BAG1, PKD1L2, and PPP2R5A) covered by rare alterations, also including three MA and four normal oral tissues. RESULTS: Fifty-seven CNAs and cnLOH were observed in the ameloblastomas and six CNAs in the AC. Seven of the CNAs were rare (six in UA and one in MA), four of them encompassing genes (gains of 7q11.21, 1q32.3, and 9p21.1 and loss of 16q23.2). We found positive correlation between rare CNA gene dosage and the expression of B4GALT1, BAG1, PKD1L2, and PPP2R5A. The AC and 1 UA were BRAF wild-type; however, this UA showed rare genomic alterations encompassing genes associated with RAF/MAPK activation. CONCLUSION: Ameloblastomas show rare CNAs and cnLOH, presenting a specific genomic profile with no overlapping of the rare alterations among UA, MA, and AC. These genomic changes might play a role in tumor evolution and in BRAFV600E-negative tumors.

HIV/HPV co-infection during pregnancy in southeastern Brazil: prevalence, HPV types, cytological abnormalities and risk factors.

OBJECTIVE: HIV(+) pregnant women are at a higher risk of HPV infection and development of cervical cancer. Our objectives were to assess the prevalence and HPV types in HIV(+) pregnant women and to identify risk factors for HPV infection and cytological abnormalities. METHODS: Cervicovaginal smears were collected during pregnancy from 140 women. Partial HPV L1 gene and the exon 4 of the human TP53 gene (containing codon 72) were PCR-amplified and sequenced. Amplified products indicating multiple HPV infection were further cloned and sequenced. The association of demographic, obstetric and HIV-related clinical variables with HPV infection and cervical lesions was tested by univariate analyses, and significant factors were subsequently tested by logistic regression multivariate analysis. RESULTS: HPV DNA tested positive for 118 patients and HPV types were identified in 104 samples. Twenty-eight different types were found, HPV-16 and HPV-58 being the most prevalent. High-risk types were present in 79.8% of samples and multiple infections in 16.3%. Abnormal cervical smears were found in 44 patients (31.4%). Absolute CD4(+) T-cell counts below 350 were associated with HPV infection. Younger age was associated with cervical abnormalities and higher CD4(+) T-cell count was an apparent protective factor. CONCLUSIONS: We found a high prevalence of HPV infection and high-risk types in this cohort. Our results highlighted the relevance of immune system integrity rather than TP53 variants for protecting this highly vulnerable population to HPV infection and carcinogenesis.