Castagnola Patrizio, Gandolfo Sergio, Malacarne Davide, Aiello Cinzia, Marino Roberto, Zoppoli Gabriele, Ballestrero Alberto, Giaretti Walter, Pentenero Monica
Department of Integrated Oncological Therapies, IRCCS AOU - San Martino - IST, Genoa, Italy.
Department of Oncology, Oral Medicine and Oral Oncology Unit, University of Turin, Turin, Italy.
PLoS One. 2017 Sep 6;12(9):e0184425. doi: 10.1371/journal.pone.0184425. eCollection 2017.
The aim of this study was to investigate the relationship between tobacco smoke habit, patient age, DNA aneuploidy and genomic DNA copy number aberrations (CNAs) in oral potentially malignant disorder (OPMD) and oral squamous cell carcinoma (OSCC) patients. DNA aneuploidy was detected by high-resolution DNA flow cytometry (hr DNA-FCM) on DAPI stained nuclei obtained from multiple tissue samples from OPMDs/OSCCs in 220 consecutive patients. Nuclear genomic aberrations were determined in a subset of 65 patients by genome-wide array comparative genomic hybridization (aCGH) using DNA extracted from either diploid or aneuploid nuclei suspension sorted by FCM. DNA aneuploidy and mean nuclear genomic aberrations were associated with patients' age. In particular, DNA aneuploidy strongly associated with age in non-smoker OPMDs/OSCCs patients. OSCCs from smokers showed a lower prevalence of DNA aneuploidy compared to OSCCs from non-smokers. A higher occurrence of DNA aneuploidy (particularly in smokers' OPMDs) was observed in patients characterized by involvement of a single oral subsite. Our study suggests that: 1) DNA aneuploidy in non-smokers is mainly related to aging; 2) OPMDs/OSCCs involving multiple oral subsites in smokers are less likely to develop DNA aneuploidy compared to non-smokers; 3) OSCC development is characterized by both CIN and CIN-independent mechanisms and that the latter are more relevant in smokers. This study provides evidence that DNA diploid OPMDs may be considered at lower risk of cancerization than DNA aneuploid ones in non-smokers but not in smokers.
本研究的目的是调查口腔潜在恶性疾病（OPMD）和口腔鳞状细胞癌（OSCC）患者的吸烟习惯、患者年龄、DNA非整倍体与基因组DNA拷贝数畸变（CNA）之间的关系。通过高分辨率DNA流式细胞术（hr DNA-FCM）对从220例连续患者的OPMD/OSCC多个组织样本中获得的经DAPI染色的细胞核进行检测，以确定DNA非整倍体情况。通过全基因组阵列比较基因组杂交（aCGH），使用从经FCM分选的二倍体或非整倍体细胞核悬液中提取的DNA，对65例患者的一个亚组进行核基因组畸变测定。DNA非整倍体和平均核基因组畸变与患者年龄相关。特别是，在不吸烟的OPMD/OSCC患者中，DNA非整倍体与年龄密切相关。与不吸烟者的OSCC相比，吸烟者的OSCC中DNA非整倍体的患病率较低。在以单个口腔亚部位受累为特征的患者中，观察到DNA非整倍体的发生率较高（尤其是在吸烟者的OPMD中）。我们的研究表明：1）不吸烟者的DNA非整倍体主要与衰老有关；2）与不吸烟者相比，吸烟者中累及多个口腔亚部位的OPMD/OSCC发生DNA非整倍体的可能性较小；3）OSCC的发生以染色体不稳定性（CIN）和非CIN依赖性机制为特征，且后者在吸烟者中更为相关。本研究提供的证据表明，在不吸烟者中，DNA二倍体OPMD发生癌变的风险可能低于DNA非整倍体OPMD，但在吸烟者中并非如此。
