Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma. / Lahtinen, Alexandra; Lavikka, Kari; Virtanen, Anni; Li, Yilin; Jamalzadeh, Sanaz; Skorda, Aikaterini; Lauridsen, Anna Røssberg; Zhang, Kaiyang; Marchi, Giovanni; Isoviita, Veli Matti; Ariotta, Valeria; Lehtonen, Oskari; Muranen, Taru A.; Huhtinen, Kaisa; Carpén, Olli; Hietanen, Sakari; Senkowski, Wojciech; Kallunki, Tuula; Häkkinen, Antti; Hynninen, Johanna; Oikkonen, Jaana; Hautaniemi, Sampsa.

In: Cancer Cell, Vol. 41, No. 6, 2023, p. 1103-1117.e12.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Lahtinen, A, Lavikka, K, Virtanen, A, Li, Y, Jamalzadeh, S, Skorda, A, Lauridsen, AR, Zhang, K, Marchi, G, Isoviita, VM, Ariotta, V, Lehtonen, O, Muranen, TA, Huhtinen, K, Carpén, O, Hietanen, S, Senkowski, W, Kallunki, T, Häkkinen, A, Hynninen, J, Oikkonen, J & Hautaniemi, S 2023, 'Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma', Cancer Cell, vol. 41, no. 6, pp. 1103-1117.e12. https://doi.org/10.1016/j.ccell.2023.04.017

APA

Lahtinen, A., Lavikka, K., Virtanen, A., Li, Y., Jamalzadeh, S., Skorda, A., Lauridsen, A. R., Zhang, K., Marchi, G., Isoviita, V. M., Ariotta, V., Lehtonen, O., Muranen, T. A., Huhtinen, K., Carpén, O., Hietanen, S., Senkowski, W., Kallunki, T., Häkkinen, A., ... Hautaniemi, S. (2023). Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma. Cancer Cell, 41(6), 1103-1117.e12. https://doi.org/10.1016/j.ccell.2023.04.017

Vancouver

Lahtinen A, Lavikka K, Virtanen A, Li Y, Jamalzadeh S, Skorda A et al. Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma. Cancer Cell. 2023;41(6):1103-1117.e12. https://doi.org/10.1016/j.ccell.2023.04.017

Author

Lahtinen, Alexandra ; Lavikka, Kari ; Virtanen, Anni ; Li, Yilin ; Jamalzadeh, Sanaz ; Skorda, Aikaterini ; Lauridsen, Anna Røssberg ; Zhang, Kaiyang ; Marchi, Giovanni ; Isoviita, Veli Matti ; Ariotta, Valeria ; Lehtonen, Oskari ; Muranen, Taru A. ; Huhtinen, Kaisa ; Carpén, Olli ; Hietanen, Sakari ; Senkowski, Wojciech ; Kallunki, Tuula ; Häkkinen, Antti ; Hynninen, Johanna ; Oikkonen, Jaana ; Hautaniemi, Sampsa. / Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma. In: Cancer Cell. 2023 ; Vol. 41, No. 6. pp. 1103-1117.e12.

Bibtex

@article{299308ce9ee04cd0afb844ba5ddd21ad,
title = "Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma",
abstract = "Ovarian high-grade serous carcinoma (HGSC) is typically diagnosed at an advanced stage, with multiple genetically heterogeneous clones existing in the tumors long before therapeutic intervention. Herein we integrate clonal composition and topology using whole-genome sequencing data from 510 samples of 148 patients with HGSC in the prospective, longitudinal, multiregion DECIDER study. Our results reveal three evolutionary states, which have distinct features in genomics, pathways, and morphological phenotypes, and significant association with treatment response. Nested pathway analysis suggests two evolutionary trajectories between the states. Experiments with five tumor organoids and three PI3K inhibitors support targeting tumors with enriched PI3K/AKT pathway with alpelisib. Heterogeneity analysis of samples from multiple anatomical sites shows that site-of-origin samples have 70% more unique clones than metastatic tumors or ascites. In conclusion, these analysis and visualization methods enable integrative tumor evolution analysis to identify patient subtypes using data from longitudinal, multiregion cohorts.",
keywords = "Cancer, Evolutionary trajectories, Integrative analysis, Multiregion sampling, Organoid experiments, Ovarian cancer, PI3K/AKT, Prospective cohort, Tumor evolution, Tumor heterogeneity",
author = "Alexandra Lahtinen and Kari Lavikka and Anni Virtanen and Yilin Li and Sanaz Jamalzadeh and Aikaterini Skorda and Lauridsen, {Anna R{\o}ssberg} and Kaiyang Zhang and Giovanni Marchi and Isoviita, {Veli Matti} and Valeria Ariotta and Oskari Lehtonen and Muranen, {Taru A.} and Kaisa Huhtinen and Olli Carp{\'e}n and Sakari Hietanen and Wojciech Senkowski and Tuula Kallunki and Antti H{\"a}kkinen and Johanna Hynninen and Jaana Oikkonen and Sampsa Hautaniemi",
note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
doi = "10.1016/j.ccell.2023.04.017",
language = "English",
volume = "41",
pages = "1103--1117.e12",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "6",

}

RIS

TY - JOUR

T1 - Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma

AU - Lahtinen, Alexandra

AU - Lavikka, Kari

AU - Virtanen, Anni

AU - Li, Yilin

AU - Jamalzadeh, Sanaz

AU - Skorda, Aikaterini

AU - Lauridsen, Anna Røssberg

AU - Zhang, Kaiyang

AU - Marchi, Giovanni

AU - Isoviita, Veli Matti

AU - Ariotta, Valeria

AU - Lehtonen, Oskari

AU - Muranen, Taru A.

AU - Huhtinen, Kaisa

AU - Carpén, Olli

AU - Hietanen, Sakari

AU - Senkowski, Wojciech

AU - Kallunki, Tuula

AU - Häkkinen, Antti

AU - Hynninen, Johanna

AU - Oikkonen, Jaana

AU - Hautaniemi, Sampsa

N1 - Publisher Copyright: © 2023 The Author(s)

PY - 2023

Y1 - 2023

N2 - Ovarian high-grade serous carcinoma (HGSC) is typically diagnosed at an advanced stage, with multiple genetically heterogeneous clones existing in the tumors long before therapeutic intervention. Herein we integrate clonal composition and topology using whole-genome sequencing data from 510 samples of 148 patients with HGSC in the prospective, longitudinal, multiregion DECIDER study. Our results reveal three evolutionary states, which have distinct features in genomics, pathways, and morphological phenotypes, and significant association with treatment response. Nested pathway analysis suggests two evolutionary trajectories between the states. Experiments with five tumor organoids and three PI3K inhibitors support targeting tumors with enriched PI3K/AKT pathway with alpelisib. Heterogeneity analysis of samples from multiple anatomical sites shows that site-of-origin samples have 70% more unique clones than metastatic tumors or ascites. In conclusion, these analysis and visualization methods enable integrative tumor evolution analysis to identify patient subtypes using data from longitudinal, multiregion cohorts.

AB - Ovarian high-grade serous carcinoma (HGSC) is typically diagnosed at an advanced stage, with multiple genetically heterogeneous clones existing in the tumors long before therapeutic intervention. Herein we integrate clonal composition and topology using whole-genome sequencing data from 510 samples of 148 patients with HGSC in the prospective, longitudinal, multiregion DECIDER study. Our results reveal three evolutionary states, which have distinct features in genomics, pathways, and morphological phenotypes, and significant association with treatment response. Nested pathway analysis suggests two evolutionary trajectories between the states. Experiments with five tumor organoids and three PI3K inhibitors support targeting tumors with enriched PI3K/AKT pathway with alpelisib. Heterogeneity analysis of samples from multiple anatomical sites shows that site-of-origin samples have 70% more unique clones than metastatic tumors or ascites. In conclusion, these analysis and visualization methods enable integrative tumor evolution analysis to identify patient subtypes using data from longitudinal, multiregion cohorts.

KW - Cancer

KW - Evolutionary trajectories

KW - Integrative analysis

KW - Multiregion sampling

KW - Organoid experiments

KW - Ovarian cancer

KW - PI3K/AKT

KW - Prospective cohort

KW - Tumor evolution

KW - Tumor heterogeneity

U2 - 10.1016/j.ccell.2023.04.017

DO - 10.1016/j.ccell.2023.04.017

M3 - Journal article

C2 - 37207655

AN - SCOPUS:85161041613

VL - 41

SP - 1103-1117.e12

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 6

ER -

ID: 357048987