Prognostic implications of a molecular classifier derived from whole-exome sequencing in nasopharyngeal carcinoma
CANCER MEDICINE
Authors: Wang, Hai-Yun; Li, Fugen; Liu, Na; Liu, Xiao-Yun; Yang, Xin-Hua; Guo, Yun-Miao; Bei, Jin-Xin; Zeng, Yi-Xin; Shao, Jian-Yong
Abstract
The aim of this study was to use whole-exome sequencing to derive a molecular classifier for nasopharyngeal carcinoma (NPC) and evaluate its clinical performance. We performed whole-exome sequencing on 82 primary NPC tumors from Sun Yat-sen University Cancer Center (Guangzhou cohort) to obtain somatic single-nucleotide variants, indels, and copy number variants. A novel molecular classifier was then developed and validated in another NPC cohort (Hong Kong cohort, n = 99). Survival analysis was estimated by the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards model was adopted for univariate and multivariate analyses. We identified three prominent NPC genetic subtypes: RAS/PI3K/AKT (based on RAS, AKT1, and PIK3CA mutations), cell-cycle (based on CDKN2A/CDKN2B deletions, and CDKN1B and CCND1 amplifications), and unclassified (based on dominant mutations in epigenetic regulators, such as KMT2C/2D, or the Notch signaling pathway, such as NOTCH1/2). These subtypes differed in survival analysis, with good, intermediate, and poor progression-free survival in the unclassified, cell-cycle, and RAS/PI3K/AKT subgroups, respectively, among the Guangzhou, Hong Kong, and combined cohorts (n = 82, P = 0.0342; n = 99, P = 0.0372; and n = 181, P = 0.0023; log-rank test). We have uncovered genetic subtypes of NPC with distinct mutations and/or copy number changes, reflecting discrete paths of NPC tumorigenesis and providing a roadmap for developing new prognostic biomarkers and targeted therapies.
Association between Cyclin D1 G870A gene polymorphism and risk of multiple myeloma
CLINICAL CANCER INVESTIGATION JOURNAL
Authors: Sabzalizadeh-Ardabili, Saeid; Hedayatizadeh-Omran, Akbar; Alizadeh-Navaei, Reza; Hosseini-Valiki, Fereshteh; Arnjadi, Omolbanin; Abbaspourkharyeki, Malek
Abstract
Background: Multiple myeloma (MM) primarily origins from terminally differentiated B cells. The Cyclin D1 (CCND1) gene polymorphism is located on the long arm of chromosome 11 in exon 4, and coding of the Cyclin D1 protein is reported in MM. This study aimed at investigating the relationship between CCND1 polymorphism and MM in northern part of Iran. Materials and Methods: This case-control study was performed on 87 patients with MM (case group) and 70 healthy individuals (control group). The population was selected from Touba Clinic, the largest referral center in Mazandaran province, Iran. Data analysis was done in SPSS software version 19. Results: The participants were aged 18-83 years (mean age: 53.8 +/- 16.7 years), including 72 (45.9%) males and 85 (54.1%) females. The adjusted odds ratio (aOR) for GG genotype was found to be significant (aOR = 4.28, confidence interval [CI] 95% = 1.21-15.13). In addition, the presence of G allele compared to allele A increased the odds ratio (OR) of MM (OR = 2.28, CI 95% = 1.45-3.57). The age and sex aOR by age and sex was 2.08, CI 95% = 1.10-3.93. Conclusion: The current study elucidated that, unlike most previous surveys on Cyclin D1 G870A gene polymorphism that associated AA genotype with various types of malignancies, the GG genotype is a risk factor for MM.