Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma—experience of the BriTROC consortium

Goranova, Teodora; Ennis, Darren; Piskorz, Anna; Macintyre, Geoff; Lewsley, Liz-Anne; Stobo, Jon; Wilson, Cheryl A.; Kay, D. W. K.; Glasspool, Rosalind; Lockley, Michelle; Brockbank, Eleanor; Montes, Ana; Walther, Axel; Sundar, Sudha; Edmondson, Richard J.; Hall, Geoff; Gourley, C.; Hall, Marcia; Fotopoulou, Christina; Gabra, Hani; Freeman, Susan; Moore, Luiza; Jimenez-Liñan, Mercedes; Paul, Jim; Brenton, James D.; McNeish, Iain A.

doi:10.1038/bjc.2017.86

Cited by 17 publications

(31 citation statements)

References 25 publications

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“…To identify copy-number (CN) signatures, we sequenced 300 primary and relapsed HGSOC samples of 142 patients from the BriTROC-1 cohort (Goranova et al, 2017) (Figure 1A). We combined low-cost shallow whole-genome sequencing (sWGS; 0.1×) with targeted amplicon sequencing of TP53 to generate absolute copy-number profiles.…”

Section: Identification and Validation Of Copy-number Signaturesmentioning

confidence: 99%

“…The BriTROC-1 study has been described previously (Goranova et al, 2017). The study is sponsored by NHS Greater Glasgow and Clyde and ethics/IRB approval was given by Cambridge Central Research Ethics Committee (Reference 12/EE/0349).…”

Section: Patients and Samplesmentioning

confidence: 99%

“…Tagged-amplicon sequencing DNA was extracted from relapsed biopsies and archival diagnostic tissue, and mutation screening of TP53 , PTEN , EGFR , PIK3CA , KRAS and BRAF was performed using tagged-amplicon sequencing as previously described (Goranova et al, 2017).…”

Section: Patients and Samplesmentioning

confidence: 99%

“…We next analysed temporal and treatment effects on copynumber signature exposure by using diagnosis and relapse samples from the BriTROC1 study ( Figure 5a, 152 samples from 116 patients, including 36 with matched sample pairs) 15 .…”

Section: Copynumber Signatures Indicate Response To Chemotherapymentioning

confidence: 99%

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Copy-number signatures and mutational processes in ovarian carcinoma

Macintyre

Goranova

Silva

et al. 2017

Preprint

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Genomic complexity from profound copynumber aberration has prevented effective molecular stratification of ovarian and other cancers. Here we present a method for copynumber signature identification that decodes this complexity. We derived eight signatures using 117 shallow wholegenome sequenced highgrade serous ovarian cancer cases, which were validated on a further 497 cases. Mutational processes underlying the copynumber signatures were identified, including breakagefusionbridge cycles, homologous recombination deficiency and wholegenome duplication. We show that most tumours are heterogeneous and harbour multiple signature exposures. We also demonstrate that copy number signatures predict overall survival and changes in signature exposure observed in response to chemotherapy suggest potential treatment strategies. 2. CC-BY-NC-ND 4.0 International license not peer-reviewed) is the author/funder. It is made available under aThe copyright holder for this preprint (which was . http://dx.doi.org/10.1101/174201 doi: bioRxiv preprint first posted online Aug. 9, 2017;The discrete mutational processes that drive copynumber change in human cancers are not readily identifiable from genomewide sequence data. This presents a major challenge for the development of precision medicine for cancers that are strongly dominated by copynumber changes, including highgrade serous ovarian (HGSOC), oesophageal, nonsmallcell lung and triple negative breast cancers 1 . These tumours have low frequency of recurrent oncogenic mutations, few recurrent copy number alterations and highly complex genomic profiles 2 .HGSOCs are poor prognosis carcinomas with ubiquitous TP53 mutation 3 . Despite efforts to discover new molecular subtypes and targeted therapies, overall survival has not improved over two decades 4 . Current genomic stratification is limited to defining homologous recombinationdeficient (HRD) tumours 57 , and classification using gene expression does not currently have clinical utility 8,9 . Detailed genomic analysis using whole genome sequencing has shown frequent loss of RB1, NF1 and PTEN by gene breakage events 10 and enrichment of amplification associated foldback inversions in nonHRD tumours 11 . However, none of these approaches has provided a broad mechanistic understanding of HGSOC, reflecting the challenges of detecting classifiers in extreme genomic complexity.Recent algorithmic advances have enabled interpretation of complex genomic changes by identifying mutational signatures genomic patterns that are the imprint of mutagenic processes accumulated over the lifetime of a cancer cell . Importantly, these studies show that tumours typically harbour multiple mutational processes requiring computational approaches that can robustly identify coexistent mutational signatures. Quantification of the exposure of a tumour to specific mutational signatures provides a rational framework to personalise therapy 14 but currently is not readily applicable to copynumber driven tumours. We hypothesized that specific feat...

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Section: Identification and Validation Of Copy-number Signaturesmentioning

confidence: 99%

Section: Patients and Samplesmentioning

confidence: 99%

Section: Patients and Samplesmentioning

confidence: 99%

Section: Copynumber Signatures Indicate Response To Chemotherapymentioning

confidence: 99%

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Copy-number signatures and mutational processes in ovarian carcinoma

Macintyre

Goranova

Silva

et al. 2017

Preprint

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“…52 Because the omentum is frequently involved by metastatic disease of gastrointestinal, genitourinary, or hematopoietic origin, establishing a tissue diagnoses is critical to triage patients into the appropriate management algorithm. 53,54 As for most other image-guided abdominal biopsies, omental and mesenteric biopsy can be performed with either US or CT guidance (►Fig. 5).…”

Section: Pancreas Biopsymentioning

confidence: 99%

Image-Guided Percutaneous Biopsy and Drainage of the Abdomen

Arellano

2018

Dig Dis Interv

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Image-guided percutaneous biopsy and abscess drainages are some of the most commonly performed procedures in interventional radiology. With advances in targeted immunotherapies for oncology patients, physicians increasingly depend on the experience and skill of the interventional radiologist to acquire tissue specimens from within the abdomen and pelvis. Furthermore, percutaneous drainage of abdominal and pelvic fluid collections has largely replaced the need for surgical interventions for infected abdominal collections. This review will discuss techniques of image-guided percutaneous abdominal biopsy and drainage.

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Targeting DNA repair: the genome as a potential biomarker

Nesic

Wakefield

Kondrashova

et al. 2018

The Journal of Pathology

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Genomic instability and mutations are fundamental aspects of human malignancies, leading to progressive accumulation of the hallmarks of cancer. For some time, it has been clear that key mutations may be used as both prognostic and predictive biomarkers, the best-known examples being the presence of germline BRCA1 or BRCA2 mutations, which are not only associated with improved prognosis in ovarian cancer, but are also predictive of response to poly(ADP-ribose) polymerase (PARP) inhibitors. Although biomarkers as specific and powerful as these are rare in human malignancies, next-generation sequencing and improved bioinformatic analyses are revealing mutational signatures, i.e. broader patterns of alterations in the cancer genome that have the power to reveal information about underlying driver mutational processes. Thus, the cancer genome can act as a stratification factor in clinical trials and, ultimately, will be used to drive personalized treatment decisions. In this review, we use ovarian high-grade serous carcinoma (HGSC) as an example of a disease of extreme genomic complexity that is marked by widespread copy number alterations, but that lacks powerful driver oncogene mutations. Understanding of the genomics of HGSC has led to the routine introduction of germline and somatic BRCA1/2 testing, as well as testing of mutations in other homologous recombination genes, widening the range of patients who may benefit from PARP inhibitors. We will discuss how whole genome-wide analyses, including loss of heterozygosity quantification and whole genome sequencing, may extend this paradigm to allow all patients to benefit from effective targeted therapies. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma—experience of the BriTROC consortium

Cited by 17 publications

References 25 publications

Copy-number signatures and mutational processes in ovarian carcinoma

Copy-number signatures and mutational processes in ovarian carcinoma

Image-Guided Percutaneous Biopsy and Drainage of the Abdomen

Targeting DNA repair: the genome as a potential biomarker

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