TY - JOUR
T1 - Distinct Genomic Profiles Are Associated with Treatment Response and Survival in Ovarian Cancer
AU - de Witte, Chris J
AU - Kutzera, Joachim
AU - van Hoeck, Arne
AU - Nguyen, Luan
AU - Boere, Ingrid A
AU - Jalving, Mathilde
AU - Ottevanger, Petronella B
AU - van Schaik-van de Mheen, Christa
AU - Stevense, Marion
AU - Kloosterman, Wigard P
AU - Zweemer, Ronald P
AU - Cuppen, Edwin
AU - Witteveen, Petronella O
N1 - Funding Information:
Funding: This research was funded by Gieskes Strijbis Foundation, grant number 1816199 and the Dutch Cancer Society, grant number UU2015-7743.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/3/2
Y1 - 2022/3/2
N2 - The majority of patients with ovarian cancer ultimately develop recurrent chemotherapy-resistant disease. Treatment stratification is mainly based on histological subtype and stage, prior response to platinum-based chemotherapy, and time to recurrent disease. Here, we integrated clinical treatment, treatment response, and survival data with whole-genome sequencing profiles of 132 solid tumor biopsies of metastatic epithelial ovarian cancer to explore genome-informed stratification opportunities. Samples from primary and recurrent disease harbored comparable numbers of single nucleotide variants and structural variants. Mutational signatures represented platinum exposure, homologous recombination deficiency, and aging. Unsupervised hierarchical clustering based on genomic input data identified specific ovarian cancer subgroups, characterized by homologous recombination deficiency, genome stability, and duplications. The clusters exhibited distinct response rates and survival probabilities which could thus potentially be used for genome-informed therapy stratification for more personalized ovarian cancer treatment.
AB - The majority of patients with ovarian cancer ultimately develop recurrent chemotherapy-resistant disease. Treatment stratification is mainly based on histological subtype and stage, prior response to platinum-based chemotherapy, and time to recurrent disease. Here, we integrated clinical treatment, treatment response, and survival data with whole-genome sequencing profiles of 132 solid tumor biopsies of metastatic epithelial ovarian cancer to explore genome-informed stratification opportunities. Samples from primary and recurrent disease harbored comparable numbers of single nucleotide variants and structural variants. Mutational signatures represented platinum exposure, homologous recombination deficiency, and aging. Unsupervised hierarchical clustering based on genomic input data identified specific ovarian cancer subgroups, characterized by homologous recombination deficiency, genome stability, and duplications. The clusters exhibited distinct response rates and survival probabilities which could thus potentially be used for genome-informed therapy stratification for more personalized ovarian cancer treatment.
KW - Ovarian cancer
KW - Patient stratification
KW - Personalized treatment
KW - Treatment response
KW - Whole-genome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85126551702&partnerID=8YFLogxK
U2 - 10.3390/cancers14061511
DO - 10.3390/cancers14061511
M3 - Article
C2 - 35326660
SN - 2072-6694
VL - 14
SP - 1
EP - 18
JO - Cancers
JF - Cancers
IS - 6
M1 - 1511
ER -