Longitudinal genomic alternations and clonal dynamics analysis of primary malignant melanoma of the esophagus

Neoplasia: An International Journal for Oncology Research

卷:30

Hongyan Wu¹  Wenyan Guan²  Chong Jiang³  Jian He³  Ziyao Liu⁴  Xiao Xiao⁵  Qing Ye⁵  Wei Ren⁶  Siyuan Liu⁶  Xiangming Quan⁷  Yiqiang Chen⁷  Zuoquan Yang⁷  Jingjing Li⁷ 

[1] Clinical Cancer Institute of Nanjing University, Nanjing 210008, China;

[2] Corresponding authors.;

[3] Geneplus-Shenzhen, Shenzhen 518118, China;

[4] The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University &

[5] The Nuclear Medicine Department of Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu, China;

[6] The Pathology Department of Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu, China;

[7] The Precision Medicine Centre of Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu, China;

关键词: Primary malignant melanoma of the esophagus;    Early dissemination;    ARHGAP35;    Dynamic evolution;   

DOI  :  

来源: DOAJ

【 摘 要 】

Primary malignant melanoma of the esophagus (PMME) is a rare gastrointestinal melanoma with a high rate of recurrence and metastasis. The standard of care for PMME has not been established yet due to a lack of understanding of its clinical and molecular pathogenesis. Thus, we performed genomic profiling on a recurrent PMME case to seek novel opportunities for the management of this rare disease. Between 2013 and 2016, 6 tissue samples including 3 from the primary tumors, 2 from the relapsed tumors, and 1 from a normal control were collected from a patient diagnosed with PMME and were subjected to whole-exome sequencing to track the dynamic genetic changes. Additionally, we also analyzed a cohort of 398 samples obtained from the TCGA skin cutanesous melanoma (TCGA-SKCM) dataset to assess the frequency and determine the clinical implications of genomic events found in the presented study. ARHGAP35 (p.L1022M) was the only mutation shared across temporal PMME lesions. The PMME samples showed higher levels of genetic instability and intra-tumor heterogeneity. They also shared several concordant copy number variations (CNV). All lesions were concordant with the evolution trajectory, and shrinkage of the founding clone caused the subclonal population to become dominant in PT1c, which was likely the reason behind metastatic seeding. ARHGAP35 mutations were found in 6% of the TCGA-SKCM cohort samples. The presence of the mutations was associated with poor progression-free survival (PFS) by both univariate and multivariate Cox regression analyses. Our study showed that the primary tumor clone disseminates earlier in PMME. This highlights the need to understand the mechanism involved in the early PMME recurrence to optimize treatment.

【 授权许可】

Unknown