Details

Autor(en) / Beteiligte

• Kang, Minsu
• Na, Hee Young
• Ahn, Soomin
• Kim, Ji-Won
• Lee, Sejoon
• Ahn, Soyeon
• Lee, Ju Hyun
• Youk, Jeonghwan
• Kim, Haesook T
• Kim, Kui-Jin
• Suh, Koung Jin
• Lee, Jun Suh
• Kim, Se Hyun
• Kim, Jin Won
• Kim, Yu Jung
• Lee, Keun-Wook
• Yoon, Yoo-Seok
• Kim, Jee Hyun
• Chung, Jin-Haeng
• Han, Ho-Seong
• Lee, Jong Seok

Titel

Gallbladder adenocarcinomas undergo subclonal diversification and selection from precancerous lesions to metastatic tumors

Ist Teil von

• eLife, 2022-12, Vol.11

Ort / Verlag

England: eLife Sciences Publications Ltd

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• We aimed to elucidate the evolutionary trajectories of gallbladder adenocarcinoma (GBAC) using multi-regional and longitudinal tumor samples. Using whole-exome sequencing data, we constructed phylogenetic trees in each patient and analyzed mutational signatures. A total of 11 patients including 2 rapid autopsy cases were enrolled. The most frequently altered gene in primary tumors was and (54.5%), followed by (27.3%). Most mutations in frequently altered genes in primary tumors were detectable in concurrent precancerous lesions (biliary intraepithelial neoplasia [BilIN]), but a substantial proportion was subclonal. Subclonal diversity was common in BilIN (n=4). However, among subclones in BilIN, a certain subclone commonly shrank in concurrent primary tumors. In addition, selected subclones underwent linear and branching evolution, maintaining subclonal diversity. Combined analysis with metastatic tumors (n=11) identified branching evolution in nine patients (81.8%). Of these, eight patients (88.9%) had a total of 11 subclones expanded at least sevenfold during metastasis. These subclones harbored putative metastasis-driving mutations in cancer-related genes such as , , and . In mutational signature analysis, six mutational signatures were identified: 1, 3, 7, 13, 22, and 24 (cosine similarity >0.9). Signatures 1 (age) and 13 (APOBEC) decreased during metastasis while signatures 22 (aristolochic acid) and 24 (aflatoxin) were relatively highlighted. Subclonal diversity arose early in precancerous lesions and clonal selection was a common event during malignant transformation in GBAC. However, selected cancer clones continued to evolve and thus maintained subclonal diversity in metastatic tumors.