Targeted DNA sequencing of high-grade serous ovarian carcinoma reveals association of TP53 mutations with platinum resistance when combined with gene expression
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064173%3A_____%2F24%3A43926832" target="_blank" >RIV/00064173:_____/24:43926832 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11120/24:43926832 RIV/00216208:11130/24:10478296 RIV/00216208:11140/24:10478296 RIV/00179906:_____/24:10478296 and 3 more
Result on the web
<a href="https://doi.org/10.1002/ijc.34908" target="_blank" >https://doi.org/10.1002/ijc.34908</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/ijc.34908" target="_blank" >10.1002/ijc.34908</a>
Alternative languages
Result language
angličtina
Original language name
Targeted DNA sequencing of high-grade serous ovarian carcinoma reveals association of TP53 mutations with platinum resistance when combined with gene expression
Original language description
High-grade serous ovarian carcinoma (HGSC) is the most common subtype of ovarian cancer and is among the most fatal gynecological malignancies worldwide, due to late diagnosis at advanced stages and frequent therapy resistance. In 47 HGSC patients, we assessed somatic and germline genetic variability of a custom panel of 144 known or suspected HGSC-related genes by high-coverage targeted DNA sequencing to identify the genetic determinants associated with resistance to platinum-based therapy. In the germline, the most mutated genes were DNAH14 (17%), RAD51B (17%), CFTR (13%), BRCA1 (11%), and RAD51 (11%). Somatically, the most mutated gene was TP53 (98%), followed by CSMD1/2/3 (19/19/36%), and CFTR (23%). Results were compared with those from whole exome sequencing of a similar set of 35 HGSC patients. Somatic variants in TP53 were also validated using GENIE data of 1287 HGSC samples. Our approach showed increased prevalence of high impact somatic and germline mutations, especially those affecting splice sites of TP53, compared to validation datasets. Furthermore, nonsense TP53 somatic mutations were negatively associated with patient survival. Elevated TP53 transcript levels were associated with platinum resistance and presence of TP53 missense mutations, while decreased TP53 levels were found in tumors carrying mutations with predicted high impact, which was confirmed in The Cancer Genome Atlas data (n = 260). Targeted DNA sequencing of TP53 combined with transcript quantification may contribute to the concept of precision oncology of HGSC. Future studies should explore targeting the p53 pathway based on specific mutation types and co-analyze the expression and mutational profiles of other key cancer genes.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
<a href="/en/project/NU20-09-00174" target="_blank" >NU20-09-00174: Importance of ovarian carcinoma genetic profile in prevention of development, progression and suboptimal treatment response</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
International Journal of Cancer
ISSN
0020-7136
e-ISSN
1097-0215
Volume of the periodical
155
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
104-116
UT code for WoS article
001180449400001
EID of the result in the Scopus database
2-s2.0-85187176229