Exome Sequencing of Paired Colorectal Carcinomas and Synchronous Liver Metastases for Prognosis and Therapy Prediction

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F23%3A10456779" target="_blank" >RIV/00216208:11140/23:10456779 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/23:43925443 RIV/00669806:_____/23:10456779

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=r9YSbKUhzB" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=r9YSbKUhzB</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1200/PO.22.00557" target="_blank" >10.1200/PO.22.00557</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Exome Sequencing of Paired Colorectal Carcinomas and Synchronous Liver Metastases for Prognosis and Therapy Prediction

Popis výsledku v původním jazyce

This study used whole exome sequencing to analyze somatic variant spectra in retrospectively collected pairs of primary tumors and synchronous liver metastases from surgically treated patients with colorectal carcinomas. Mutational profiles served for comparing groups of patients stratified by response to chemotherapy and survival. The study utilized sample pairs from 20 patients diagnosed and treated at a single center. The most frequently altered oncodrivers were APC (55% in primaries and 60% in metastases), TP53 (50/45), TRIP11 (30/5), FAT4 (20/25), and KRAS (15/25). A high load of variants with high predicted effect (i.e., mainly frameshift, splice site, and nonsense) was associated with prolonged relapse-free survival while the opposite was observed for variants with moderate effect (i.e., mostly missense). Variants in individual genes, e.g., ATM, KRAS, and MUC5AC or oncodriver pathways represented poor prognostic factors with significant differences between primary tumor and metastasis. No gene or profile was significantly associated with the response to chemotherapy. Taken together, we report subtle differences in exome mutational profiles between paired primary tumors and synchronous liver metastases except for TRIP11 and several putative prognostic genes and profiles. After functional characterization, our data may provide a lead for studies focused on utilizing these findings in precision oncology.

Název v anglickém jazyce

Exome Sequencing of Paired Colorectal Carcinomas and Synchronous Liver Metastases for Prognosis and Therapy Prediction

Popis výsledku anglicky

This study used whole exome sequencing to analyze somatic variant spectra in retrospectively collected pairs of primary tumors and synchronous liver metastases from surgically treated patients with colorectal carcinomas. Mutational profiles served for comparing groups of patients stratified by response to chemotherapy and survival. The study utilized sample pairs from 20 patients diagnosed and treated at a single center. The most frequently altered oncodrivers were APC (55% in primaries and 60% in metastases), TP53 (50/45), TRIP11 (30/5), FAT4 (20/25), and KRAS (15/25). A high load of variants with high predicted effect (i.e., mainly frameshift, splice site, and nonsense) was associated with prolonged relapse-free survival while the opposite was observed for variants with moderate effect (i.e., mostly missense). Variants in individual genes, e.g., ATM, KRAS, and MUC5AC or oncodriver pathways represented poor prognostic factors with significant differences between primary tumor and metastasis. No gene or profile was significantly associated with the response to chemotherapy. Taken together, we report subtle differences in exome mutational profiles between paired primary tumors and synchronous liver metastases except for TRIP11 and several putative prognostic genes and profiles. After functional characterization, our data may provide a lead for studies focused on utilizing these findings in precision oncology.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

JCO Precision Oncology

ISSN

2473-4284

e-ISSN

2473-4284

Svazek periodika

7

Číslo periodika v rámci svazku

May

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

e2200557

Kód UT WoS článku

001184686900001

EID výsledku v databázi Scopus

2-s2.0-85176930117