Abstract：
UNASSIGNED: A minority of patients with MSS tumors present a high tumor mutation burden (TMB) without underlying MMR defects.
UNASSIGNED: Publicly available genomic series were assessed for identification of patients with MSS gastric gastroesophageal junction, and esophageal adenocarcinomas and a high TMB, defined as more than 10 mutations per Mb. These were compared with MSS cancers and a low TMB for genetic alterations and for survival outcomes.
UNASSIGNED: Patients with MSS cancers with high TMB in the MSK series were older but did not differ in other clinicopathologic parameters compared with MSS patients with low TMB. Mutations in tumor suppressors TP53 and APC and oncogenes KRAS and ERBB4 as well as amplifications of ERBB2 were more prevalent in the high TMB group of MSS cancers. Mutations in DDR associated genes, in epigenetic modifiers and in genes associated with immune response were more prevalent in the hIgh TMB group patients. However, high TMB was not associated with an improved survival in MSS gastric/gastroesophageal junction/esophageal adenocarcinomas (Log Rank p = 0.5).
UNASSIGNED: MSS Gastric/gastroesophageal junction/esophageal adenocarcinomas with TMB above 10 mutations per Mb possess a genomic landscape with increased alteration frequencies in common gastroesophageal cancer genes and pathways.
UNASSIGNED: Publicly available genomic series were assessed for identification of patients with MSS gastric gastroesophageal junction, and esophageal adenocarcinomas and a high TMB, defined as more than 10 mutations per Mb. These were compared with MSS cancers and a low TMB for genetic alterations and for survival outcomes.
UNASSIGNED: Patients with MSS cancers with high TMB in the MSK series were older but did not differ in other clinicopathologic parameters compared with MSS patients with low TMB. Mutations in tumor suppressors TP53 and APC and oncogenes KRAS and ERBB4 as well as amplifications of ERBB2 were more prevalent in the high TMB group of MSS cancers. Mutations in DDR associated genes, in epigenetic modifiers and in genes associated with immune response were more prevalent in the hIgh TMB group patients. However, high TMB was not associated with an improved survival in MSS gastric/gastroesophageal junction/esophageal adenocarcinomas (Log Rank p = 0.5).
UNASSIGNED: MSS Gastric/gastroesophageal junction/esophageal adenocarcinomas with TMB above 10 mutations per Mb possess a genomic landscape with increased alteration frequencies in common gastroesophageal cancer genes and pathways.
摘要：
■少数患有MSS肿瘤的患者呈现高肿瘤突变负荷(TMB)而没有潜在的MMR缺陷。
■评估了公开可用的基因组系列，以鉴定MSS胃食管交界处的患者，食管腺癌和高TMB，定义为每Mb超过10个突变。将这些与MSS癌症和低TMB的遗传改变和生存结果进行比较。
MSK系列中TMB较高的MSS癌症患者年龄较大，但与TMB较低的MSS患者相比，其他临床病理参数没有差异。肿瘤抑制因子TP53和APC和癌基因KRAS和ERBB4的突变以及ERBB2的扩增在MSS癌症的高TMB组中更为普遍。DDR相关基因突变，在表观遗传修饰因子和与免疫反应相关的基因中，在hIghTMB组患者中更为普遍。然而,在MSS胃/胃食管交界处/食管腺癌中,高TMB与生存率改善无关(LogRankp=0.5).
■MSS胃/胃食管交界处/食管腺癌TMB超过10个突变/Mb，具有常见胃食管癌基因和通路改变频率增加的基因组景观。
■评估了公开可用的基因组系列，以鉴定MSS胃食管交界处的患者，食管腺癌和高TMB，定义为每Mb超过10个突变。将这些与MSS癌症和低TMB的遗传改变和生存结果进行比较。
MSK系列中TMB较高的MSS癌症患者年龄较大，但与TMB较低的MSS患者相比，其他临床病理参数没有差异。肿瘤抑制因子TP53和APC和癌基因KRAS和ERBB4的突变以及ERBB2的扩增在MSS癌症的高TMB组中更为普遍。DDR相关基因突变，在表观遗传修饰因子和与免疫反应相关的基因中，在hIghTMB组患者中更为普遍。然而,在MSS胃/胃食管交界处/食管腺癌中,高TMB与生存率改善无关(LogRankp=0.5).
■MSS胃/胃食管交界处/食管腺癌TMB超过10个突变/Mb，具有常见胃食管癌基因和通路改变频率增加的基因组景观。
