The molecular events and transcriptional plasticity driving brain metastasis in clinically relevant breast tumor subtypes has not been determined. Here we comprehensively dissect genomic, transcriptomic and clinical data in patient-matched longitudinal tumor samples, and unravel distinct transcriptional programs enriched in brain metastasis. We report on subtype specific hub genes and functional processes, central to disease-affected networks in brain metastasis. Importantly, in luminal brain metastases we identify homologous recombination deficiency operative in transcriptomic and genomic data with recurrent breast mutational signatures A, F and K, associated with mismatch repair defects, TP53 mutations and homologous recombination deficiency (HRD) respectively. Utilizing PARP inhibition in patient-derived brain metastatic tumor explants we functionally validate HRD as a key vulnerability. Here, we demonstrate a functionally relevant HRD evident at genomic and transcriptomic levels pointing to genomic instability in breast cancer brain metastasis which is of potential translational significance.
Oral squamous papillomas are benign proliferating lesions induced by human papilloma virus. These lesions are painless and slowly growing masses. As an oral lesion, it raises concern because of its clinical appearance. These lesions commonly occur between age 30 and 50 years, and sometimes can occur before the age of 10 years. Oral squamous papilloma accounts for 8% of all oral tumors in children. Common site predilection for the lesion is the tongue and soft palate, and may occur on any other surface of the oral cavity such as the uvula and vermilion of the lip. Here, we are presenting a case of squamous papilloma on the palate.
Summary In a study of factors related to cervical carcinogenesis, a cohort of 1,107 cervical dysplasia along with 1,077 controls matched for age and parity were followed up prospectively. During the follow up 75 dysplasia cases progressed to carcinoma in situ. The overall rate of progression of dysplasia to malignancy was observed to be 15.7% at the end of 108 months of follow-up. The Dysplasia subjects and their husbands were contacted by a team of trained medical social workers and gynaecologists to educate them about the objectives of the study and to elicit their co-operation. All the subjects agreed to participate in the study.Base line information andfollow-up The details of subject selection and investigational procedure have been described earlier (Luthra et al., 1987
In a hospital-based cytology screening programme for the early detection of preinvasive lesions of the uterine cervix, 166 women with abnormal smears (human papillomavirus (HPV) changes, cervical intraepithelial neoplasia (CIN) and invasive carcinoma) were referred to the central colposcopy clinic between January 1989 and December 1991. The colposcopist (V.S.) was able to take a direct biopsy in 156 cases. In the remaining 10-cases, biopsy could not be taken because of unsatisfactory colposcopy. A cytohistological correlation was obtained in 121/156 (77.5%) cases, and the remaining 35 cases showed a disparity in diagnosis. These were reviewed by one of us (P.S.) and the reasons for underdiagnosis/false negatives and overdiagnosis/false-positive results were analysed. It was found that sampling error was the cause of false negativity and underdiagnosis in most cases while interpretative errors resulted in the overdiagnosis and false-positive smears. The reasons for interpretative errors were studied in detail.
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