Somatic copy number alterations (sCNAs) are a type of genomic variation that affects the dosage of DNA sequences promoting tumorigenesis such as in High grade serous ovarian cancer. Their complexity prevents the unravelling of the mechanisms generating them and the molecular stratification of the patients. Here we propose the implementation of a highly sensitive pipeline for their detection based on structural variant calling and a signature analysis for the extraction of recurrent patterns. The precise calling allowed the recovery of small segments missed from the previous pipeline and in turn the clear distinction of patients with Homologous Recombination Deficiency (HRD), which resulted extremely segmented. Although the signature analysis, based on COSMIC copy number signatures, did not provide results consistent with the clinical data, the de novo signature extraction provided 15 new signatures able to proficiently explain the dataset. Two of them were positively associated with HRD, possibly representing a test for the identification of the HRD phenotype. Further insights on these signatures may provide the discovery of their etiology and give the possibility to shed light on association with single nucleotide variations.

Somatic copy number alterations (sCNAs) are a type of genomic variation that affects the dosage of DNA sequences promoting tumorigenesis such as in High grade serous ovarian cancer. Their complexity prevents the unravelling of the mechanisms generating them and the molecular stratification of the patients. Here we propose the implementation of a highly sensitive pipeline for their detection based on structural variant calling and a signature analysis for the extraction of recurrent patterns. The precise calling allowed the recovery of small segments missed from the previous pipeline and in turn the clear distinction of patients with Homologous Recombination Deficiency (HRD), which resulted extremely segmented. Although the signature analysis, based on COSMIC copy number signatures, did not provide results consistent with the clinical data, the de novo signature extraction provided 15 new signatures able to proficiently explain the dataset. Two of them were positively associated with HRD, possibly representing a test for the identification of the HRD phenotype. Further insights on these signatures may provide the discovery of their etiology and give the possibility to shed light on association with single nucleotide variations.

Somatic Copy Number Alteration detection and Copy Number signature analysis in High-Grade Serous Ovarian Cancer

MICOLI, GIULIA
2021/2022

Abstract

Somatic copy number alterations (sCNAs) are a type of genomic variation that affects the dosage of DNA sequences promoting tumorigenesis such as in High grade serous ovarian cancer. Their complexity prevents the unravelling of the mechanisms generating them and the molecular stratification of the patients. Here we propose the implementation of a highly sensitive pipeline for their detection based on structural variant calling and a signature analysis for the extraction of recurrent patterns. The precise calling allowed the recovery of small segments missed from the previous pipeline and in turn the clear distinction of patients with Homologous Recombination Deficiency (HRD), which resulted extremely segmented. Although the signature analysis, based on COSMIC copy number signatures, did not provide results consistent with the clinical data, the de novo signature extraction provided 15 new signatures able to proficiently explain the dataset. Two of them were positively associated with HRD, possibly representing a test for the identification of the HRD phenotype. Further insights on these signatures may provide the discovery of their etiology and give the possibility to shed light on association with single nucleotide variations.
2021
Somatic Copy Number Alteration detection and Copy Number signature analysis in High-Grade Serous Ovarian Cancer
Somatic copy number alterations (sCNAs) are a type of genomic variation that affects the dosage of DNA sequences promoting tumorigenesis such as in High grade serous ovarian cancer. Their complexity prevents the unravelling of the mechanisms generating them and the molecular stratification of the patients. Here we propose the implementation of a highly sensitive pipeline for their detection based on structural variant calling and a signature analysis for the extraction of recurrent patterns. The precise calling allowed the recovery of small segments missed from the previous pipeline and in turn the clear distinction of patients with Homologous Recombination Deficiency (HRD), which resulted extremely segmented. Although the signature analysis, based on COSMIC copy number signatures, did not provide results consistent with the clinical data, the de novo signature extraction provided 15 new signatures able to proficiently explain the dataset. Two of them were positively associated with HRD, possibly representing a test for the identification of the HRD phenotype. Further insights on these signatures may provide the discovery of their etiology and give the possibility to shed light on association with single nucleotide variations.
Copy Number
Mutational signature
Ovarian Cancer
File in questo prodotto:
File Dimensione Formato  
Micoli_Giulia.pdf

accesso aperto

Dimensione 13.85 MB
Formato Adobe PDF
13.85 MB Adobe PDF Visualizza/Apri

The text of this website © Università degli studi di Padova. Full Text are published under a non-exclusive license. Metadata are under a CC0 License

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12608/34058