Low frequency of cancer-predisposition gene mutations in liver transplant candidates with hepatocellular carcinoma

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F23%3A00083549" target="_blank" >RIV/00023001:_____/23:00083549 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/23:10453998 RIV/00216208:11110/23:10453998 RIV/00064165:_____/23:10453998

Result on the web

<a href="https://www.mdpi.com/2072-6694/15/1/201" target="_blank" >https://www.mdpi.com/2072-6694/15/1/201</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cancers15010201" target="_blank" >10.3390/cancers15010201</a>

Result language

angličtina

Original language name

Low frequency of cancer-predisposition gene mutations in liver transplant candidates with hepatocellular carcinoma

Original language description

Simple Summary Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths worldwide. HCC mostly results from liver cirrhosis and its genetic predisposition is believed to be rare. A liver transplantation is considered a curative therapy for HCC; however, de novo tumor development is a feared complication in immunosuppressed transplant recipients. Having analyzed the prevalence of pathogenic/likely pathogenic germline variants in cancer-predisposition genes in 334 HCC patients considered for liver transplantation, we found only 7/334 (2.1%) carriers of pathogenic variants in established cancer-predisposition genes (PMS2, 4xNBN, FH or RET). Interestingly, two MRN complex genes (NBN and RAD50) were significantly more frequent among patients over controls. Therefore, we conclude that the genetic predisposition to HCC is rare and HCC does not meet the criteria for routine germline genetic testing; however, germline testing could be considered in liver transplant recipients as the variant carriers may benefit from tailored follow-up or targeted therapy. Hepatocellular carcinoma (HCC) mainly stems from liver cirrhosis and its genetic predisposition is believed to be rare. However, two recent studies describe pathogenic/likely pathogenic germline variants (PV) in cancer-predisposition genes (CPG). As the risk of de novo tumors might be increased in PV carriers, especially in immunosuppressed patients after a liver transplantation, we analyzed the prevalence of germline CPG variants in HCC patients considered for liver transplantation. Using the panel NGS targeting 226 CPGs, we analyzed germline DNA from 334 Czech HCC patients and 1662 population-matched controls. We identified 48 PVs in 35 genes in 47/334 patients (14.1%). However, only 7/334 (2.1%) patients carried a PV in an established CPG (PMS2, 4xNBN, FH or RET). Only the PV carriers in two MRN complex genes (NBN and RAD50) were significantly more frequent among patients over controls. We found no differences in clinicopathological characteristics between carriers and non-carriers. Our study indicated that the genetic component of HCC is rare. The HCC diagnosis itself does not meet criteria for routine germline CPG genetic testing. However, a low proportion of PV carriers may benefit from a tailored follow-up or targeted therapy and germline testing could be considered in liver transplant recipients.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30219 - Gastroenterology and hepatology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

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

Name of the periodical

Cancers

ISSN

2072-6694

e-ISSN

2072-6694

Volume of the periodical

15

Issue of the periodical within the volume

1

Country of publishing house

CH - SWITZERLAND

Number of pages

14

Pages from-to

"art. no. 201"

UT code for WoS article

000908874100001

EID of the result in the Scopus database

2-s2.0-85146028628