Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW, Australia.
Genes Chromosomes Cancer. 2022 Sep;61(9):561-571. doi: 10.1002/gcc.23076. Epub 2022 Jun 24.
Oral squamous cell carcinoma (OSCC) in the young (<50 years), without known carcinogenic risk factors, is on the rise globally. Whole genome duplication (WGD) has been shown to occur at higher rates in cancers without an identifiable carcinogenic agent. We aimed to evaluate the prevalence of WGD in a cohort of OSCC patients under the age of 50 years.
Whole genome sequencing (WGS) was performed on 28 OSCC patients from the Sydney Head and Neck Cancer Institute (SHNCI) biobank. An additional nine cases were obtained from The Cancer Genome Atlas (TCGA).
WGD was seen in 27 of 37 (73%) cases. Non-synonymous, somatic TP53 mutations occurred in 25 of 27 (93%) cases of WGD and were predicted to precede WGD in 21 (77%). WGD was significantly associated with larger tumor size (p = 0.01) and was frequent in patients with recurrences (87%, p = 0.36). Overall survival was significantly worse in those with WGD (p = 0.05).
Our data, based on one of the largest WGS datasets of young patients with OSCC, demonstrates a high frequency of WGD and its association with adverse pathologic characteristics and clinical outcomes. TP53 mutations also preceded WGD, as has been described in other tumors without a clear mutagenic driver.
在全球范围内，年轻（<50 岁）且无已知致癌风险因素的口腔鳞状细胞癌（OSCC）发病率正在上升。在没有明确致癌剂的癌症中，全基因组倍增（WGD）的发生率更高。我们旨在评估年轻（<50 岁）OSCC 患者队列中 WGD 的发生率。
对来自悉尼头颈部癌症研究所（SHNCI）生物库的 28 名 OSCC 患者进行全基因组测序（WGS）。另外从癌症基因组图谱（TCGA）中获得了 9 例病例。
在 37 例（73%）病例中观察到 WGD。27 例 WGD 中有 25 例（93%）发生非同义体细胞 TP53 突变，其中 21 例（77%）突变预测发生在 WGD 之前。WGD 与更大的肿瘤大小显著相关（p=0.01），在复发患者中更为常见（87%，p=0.36）。WGD 患者的总体生存率明显较差（p=0.05）。
我们的数据基于年轻 OSCC 患者最大的 WGS 数据集之一，表明 WGD 发生率较高，并且与不良病理特征和临床结果相关。TP53 突变也先于 WGD 发生，这在其他没有明确诱变驱动因素的肿瘤中已有描述。
