Boqiang Fan1, Xianfeng Xu2, Xuehao Wang3. 1. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, Jiangsu Province, China. 2. Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China. 3. Key Laboratory of Liver Transplantation, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Chinese Academy of Medical Sciences, Nanjing, Jiangsu Province, China. wangxh@njmu.edu.cn.
Abstract
BACKGROUND: Comprehensive genomic analysis of paired primary tumors and their metastatic lesions may provide new insights into the biology of metastatic processes and therefore guide the development of novel strategies for intervention. To date, our knowledge of the genetic divergence and phylogenetic relationships in gallbladder cancer (GBC) is limited. METHODS: We performed whole exome sequencing for 5 patients with primary tumor, metastatic lymph node (LNM) and corresponding normal tissue. Mutations, mutation signatures and copy number variations were analyzed with state-of-art bioinformatics methods. Phylogenetic tree was also generated to infer metastatic pattern. RESULTS: Five driver mutations were detected in these patients. Among which, TP53 was the only shared mutation between primary tumor and LNM. Although tumor mutational burden was comparable between primary tumor and LNM, higher mutation burden was observed in LNM of one patient. Copy number variations (CNVs) burden was higher in LNM than their primary tumor. Phylogenetic analysis indicated both linear and parallel progression of metastasis exist in these patients. TP53 mutation and CNVs were homogenously between primary tumor and LNM. CONCLUSIONS: High consistence of genetic landscape were shown between primary tumor and LNM in GBC. However, heterogenicity still exist between primary tumor and LNM in particular patients in term of driver mutation, TMB and CNV burden. Phylogenetic analysis indicated both Linear and parallel progression of metastasis were exist among these patients.
BACKGROUND: Comprehensive genomic analysis of paired primary tumors and their metastatic lesions may provide new insights into the biology of metastatic processes and therefore guide the development of novel strategies for intervention. To date, our knowledge of the genetic divergence and phylogenetic relationships in gallbladder cancer (GBC) is limited. METHODS: We performed whole exome sequencing for 5 patients with primary tumor, metastatic lymph node (LNM) and corresponding normal tissue. Mutations, mutation signatures and copy number variations were analyzed with state-of-art bioinformatics methods. Phylogenetic tree was also generated to infer metastatic pattern. RESULTS: Five driver mutations were detected in these patients. Among which, TP53 was the only shared mutation between primary tumor and LNM. Although tumor mutational burden was comparable between primary tumor and LNM, higher mutation burden was observed in LNM of one patient. Copy number variations (CNVs) burden was higher in LNM than their primary tumor. Phylogenetic analysis indicated both linear and parallel progression of metastasis exist in these patients. TP53 mutation and CNVs were homogenously between primary tumor and LNM. CONCLUSIONS: High consistence of genetic landscape were shown between primary tumor and LNM in GBC. However, heterogenicity still exist between primary tumor and LNM in particular patients in term of driver mutation, TMB and CNV burden. Phylogenetic analysis indicated both Linear and parallel progression of metastasis were exist among these patients.
Authors: A Duffy; M Capanu; G K Abou-Alfa; D Huitzil; W Jarnagin; Y Fong; M D'Angelica; R P Dematteo; L H Blumgart; E M O'Reilly Journal: J Surg Oncol Date: 2008-12-01 Impact factor: 3.454
Authors: Yuchen Jiao; Timothy M Pawlik; Robert A Anders; Florin M Selaru; Mirte M Streppel; Donald J Lucas; Noushin Niknafs; Violeta Beleva Guthrie; Anirban Maitra; Pedram Argani; G Johan A Offerhaus; Juan Carlos Roa; Lewis R Roberts; Gregory J Gores; Irinel Popescu; Sorin T Alexandrescu; Simona Dima; Matteo Fassan; Michele Simbolo; Andrea Mafficini; Paola Capelli; Rita T Lawlor; Andrea Ruzzenente; Alfredo Guglielmi; Giampaolo Tortora; Filippo de Braud; Aldo Scarpa; William Jarnagin; David Klimstra; Rachel Karchin; Victor E Velculescu; Ralph H Hruban; Bert Vogelstein; Kenneth W Kinzler; Nickolas Papadopoulos; Laura D Wood Journal: Nat Genet Date: 2013-11-03 Impact factor: 38.330