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Low homozygous/high heterozygous deletion status by p16 FISH correlates with a better prognostic group than high homozygous deletion status in malignant pleural mesothelioma

التفاصيل البيبلوغرافية
العنوان: Low homozygous/high heterozygous deletion status by p16 FISH correlates with a better prognostic group than high homozygous deletion status in malignant pleural mesothelioma
المؤلفون: Shinji Matsumoto, Kenzo Hiroshima, Kazuki Nabeshima, Ayuko Sato, Sousei Abe, Kunimitsu Kawahara, Makoto Hamasaki, Yukio Nakatani, Yasuhiro Yoshida, Tohru Tsujimura, Toshiaki Kamei, Daisuke Hamatake, Akinori Iwasaki
المصدر: Lung Cancer. 99:155-161
بيانات النشر: Elsevier BV, 2016.
سنة النشر: 2016
مصطلحات موضوعية: Adult, Male, Mesothelioma, 0301 basic medicine, Pulmonary and Respiratory Medicine, Heterozygote, Cancer Research, Lung Neoplasms, Adolescent, Genotype, Pleural Neoplasms, Bisulfite sequencing, Gene Dosage, Biology, law.invention, Young Adult, 03 medical and health sciences, Mesothelial hyperplasia, 0302 clinical medicine, law, CDKN2A, medicine, Humans, Genetic Predisposition to Disease, Allele, Genetic Association Studies, In Situ Hybridization, Fluorescence, Polymerase chain reaction, Aged, Aged, 80 and over, medicine.diagnostic_test, Genes, p16, Homozygote, Mesothelioma, Malignant, Middle Aged, Prognosis, Survival Analysis, Molecular biology, Log-rank test, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Fish , Female, Gene Deletion, Fluorescence in situ hybridization
الوصف: Objectives Homozygous deletion (homo-d) of the p16 (CDKN2A) gene, as determined by fluorescence in situ hybridization (FISH), helps differentiate malignant pleural mesothelioma (MPM) from reactive mesothelial hyperplasia (RMH). Heterozygous deletion (hetero-d) has also been identified variably in p16 FISH. This study aimed to investigate the significance of homo-d and hetero-d of p16 in the diagnosis and prognosis of MPM. Materials and methods p16 FISH was performed in 93 MPMs and 47 RMHs. Real-time polymerase chain reaction (PCR) and methylation specific PCR (MSP) were also performed for cases in which DNA was available. Overall survival (OS) was assessed via the Kaplan-Meier method and logrank test. Results Cutoff values for homo-d and hetero-d were set at 10% and 47%, respectively, based on p16 FISH results in RMH. In MPM, 80/93 (86.0%) were homo-d positive, and 15/93 (16.1%) were hetero-d positive. No RMH was homo/hetero-d positive. In nine cases of MPM with the low homo-d ( 47%) pattern, FISH with a shorter probe caused a slight increase (from 20.1% to 26.5%) in the mean percentage of homo-d and a decrease in that of hetero-d (from 59.6% to 55.6%). Four cases in which the low homo-d/high hetero-d pattern was maintained with the shorter probe were further analyzed by real-time PCR, which separated them into a two (n = 2) or one allele deletion group (n = 2). MSP revealed no promoter methylation in the two cases with one allele deletion. The OS was significantly shorter in homo-d positive cases (n = 24) than homo-d negative cases (n = 5, p = 0.0002) in the 29 MPM cases with follow-up data. Also, low homo-d/high hetero-d cases (n = 5) had a significantly better prognosis than high homo-d (≥30%) cases (n = 17, p = 0.011). Conclusions Within p16 homo-d positive MPMs with poorer prognosis, the low homo-d/high hetero-d pattern may belong to a better prognostic subgroup in homo-d positive MPMs.
تدمد: 0169-5002
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b1477181fd97b4ecaf303e5eed19b72d
https://doi.org/10.1016/j.lungcan.2016.07.011
حقوق: CLOSED
رقم الأكسشن: edsair.doi.dedup.....b1477181fd97b4ecaf303e5eed19b72d
قاعدة البيانات: OpenAIRE
الوصف
تدمد:01695002