Distinct mutational backgrounds and clonal architectures implicated prognostic discrepancies in small-cell carcinomas of the esophagus and lung

Abstract Small-cell carcinoma of the esophagus (SCCE) is a rare and aggressive cancer. Although several consistent genomic changes were observed previously between SCCE and small-cell lung cancer (SCLC), detailed mutational landscapes revealing discrepancies in genetic underpinnings of tumorigenesis...

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Main Authors: Zhengbo Song, Yueping Liu, Guoping Cheng, Lianpeng Chang, Zicheng Yu, Ming Chen, Gang Chen
Format: Article
Language:English
Published: Nature Publishing Group 2021-05-01
Series:Cell Death and Disease
Online Access:https://doi.org/10.1038/s41419-021-03754-0
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spelling doaj-f9aa163cc7a14043bdb7cfd0927dc3b92021-05-16T11:04:57ZengNature Publishing GroupCell Death and Disease2041-48892021-05-011251810.1038/s41419-021-03754-0Distinct mutational backgrounds and clonal architectures implicated prognostic discrepancies in small-cell carcinomas of the esophagus and lungZhengbo Song0Yueping Liu1Guoping Cheng2Lianpeng Chang3Zicheng Yu4Ming Chen5Gang Chen6Department of Clinical Trial, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of SciencesDepartment of Pathology, Hebei Cancer HospitalDepartment of Pathology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of SciencesGeneplus-Beijing InstituteGeneplus-Beijing InstituteDepartment of Radiotherapy, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of SciencesDepartment of Pathology, Fujian Medical University Cancer Hospital and Fujian Cancer HospitalAbstract Small-cell carcinoma of the esophagus (SCCE) is a rare and aggressive cancer. Although several consistent genomic changes were observed previously between SCCE and small-cell lung cancer (SCLC), detailed mutational landscapes revealing discrepancies in genetic underpinnings of tumorigenesis between these two cancers are scarce, and little attention has been paid to answer whether these genetic alterations were related to the prognosis. Herein by performing whole-exome sequencing of 48 SCCE and 64 SCLC tumor samples, respectively we have shown that the number of driver mutations in SCCE was significantly lower than in SCLC (p = 0.0042). In SCCE, 46% of recurrent driver mutations were clonal, which occurred at an early stage during tumorigenesis, while 16 driver mutations were found clonal in SCLC. NOTCH1/3, PIK3CA, and ATM were specifically clonal in SCCE, while TP53 was clonal in SCLC. The total number of clonal mutations differed between two cancers and presented lower in SCCE compared to SCLC (p = 0.0036). Moreover, overall survival (OS) was shorter in patients with higher numbers of clonal mutations for both cancers. In summary, SCCE showed distinct mutational background and clonal architecture compared with SCLC. Organ-specific clonal events revealed different molecular mechanisms underlying tumorigenesis, tumor development, patients’ prognosis, and possible variations in therapeutic outcomes to candidate treatments.https://doi.org/10.1038/s41419-021-03754-0
collection DOAJ
language English
format Article
sources DOAJ
author Zhengbo Song
Yueping Liu
Guoping Cheng
Lianpeng Chang
Zicheng Yu
Ming Chen
Gang Chen
spellingShingle Zhengbo Song
Yueping Liu
Guoping Cheng
Lianpeng Chang
Zicheng Yu
Ming Chen
Gang Chen
Distinct mutational backgrounds and clonal architectures implicated prognostic discrepancies in small-cell carcinomas of the esophagus and lung
Cell Death and Disease
author_facet Zhengbo Song
Yueping Liu
Guoping Cheng
Lianpeng Chang
Zicheng Yu
Ming Chen
Gang Chen
author_sort Zhengbo Song
title Distinct mutational backgrounds and clonal architectures implicated prognostic discrepancies in small-cell carcinomas of the esophagus and lung
title_short Distinct mutational backgrounds and clonal architectures implicated prognostic discrepancies in small-cell carcinomas of the esophagus and lung
title_full Distinct mutational backgrounds and clonal architectures implicated prognostic discrepancies in small-cell carcinomas of the esophagus and lung
title_fullStr Distinct mutational backgrounds and clonal architectures implicated prognostic discrepancies in small-cell carcinomas of the esophagus and lung
title_full_unstemmed Distinct mutational backgrounds and clonal architectures implicated prognostic discrepancies in small-cell carcinomas of the esophagus and lung
title_sort distinct mutational backgrounds and clonal architectures implicated prognostic discrepancies in small-cell carcinomas of the esophagus and lung
publisher Nature Publishing Group
series Cell Death and Disease
issn 2041-4889
publishDate 2021-05-01
description Abstract Small-cell carcinoma of the esophagus (SCCE) is a rare and aggressive cancer. Although several consistent genomic changes were observed previously between SCCE and small-cell lung cancer (SCLC), detailed mutational landscapes revealing discrepancies in genetic underpinnings of tumorigenesis between these two cancers are scarce, and little attention has been paid to answer whether these genetic alterations were related to the prognosis. Herein by performing whole-exome sequencing of 48 SCCE and 64 SCLC tumor samples, respectively we have shown that the number of driver mutations in SCCE was significantly lower than in SCLC (p = 0.0042). In SCCE, 46% of recurrent driver mutations were clonal, which occurred at an early stage during tumorigenesis, while 16 driver mutations were found clonal in SCLC. NOTCH1/3, PIK3CA, and ATM were specifically clonal in SCCE, while TP53 was clonal in SCLC. The total number of clonal mutations differed between two cancers and presented lower in SCCE compared to SCLC (p = 0.0036). Moreover, overall survival (OS) was shorter in patients with higher numbers of clonal mutations for both cancers. In summary, SCCE showed distinct mutational background and clonal architecture compared with SCLC. Organ-specific clonal events revealed different molecular mechanisms underlying tumorigenesis, tumor development, patients’ prognosis, and possible variations in therapeutic outcomes to candidate treatments.
url https://doi.org/10.1038/s41419-021-03754-0
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