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Table 3 Summary of included articles in the systematic review

From: Evolutionary perspectives, heterogeneity and ovarian cancer: a complicated tale from past to present

First author Year Cohort Method Conclusion Ref
Taylor HC 1959 550 samples from 36 patients and 12 temporal paired samples Light microscopy Consistent morphology across tumor areas and at relapse [25]
Knoerr-Gaertner H 1977 4 cases of bilateral cystadenocarcinomas Chromosomal banding Identical chromosomal markers found in bilateral cystadenocarcinomas without definite proof for clonal or multicentric evolution [26]
Roberts CG 1990 3 samples from 1 case Chromosomal banding and inferred clonal cytogenetic evolution First report of clonal evolution based on chromosomal breakpoints analysis [28]
Pejovic T 1991 34 samples from 15 cases Chromosomal banding No evolution seen in spatially separated samples. Possible explanations given: metastatic spread is a late event in evolution, identical evolution in paired samples, clonal dominance of cells with growth advantage [27]
Vandamme B 1992 17 samples from 6 cases and 4 temporal samples from 1 case Restriction fragment length polymorphism 11p deletion is a late event in disease progression [30]
Abeln ECA 1994 3 cases Flow cytometry and PCR on microsatellite markers Proof of principle PCR-based LOH detection on flow sorted tumor cells can determine their monoclonal origin and can be used for the analysis of tumor heterogeneity [32]
Deger RB 1997 21 samples from 8 cases Chromosomal banding 50% of cases had less complex chromosomal aberrations in metastatic lesions [34]
Ioakim-Liossi A 1999 9 patients with paired temporal samples Chromosomal banding Identical chromosomal aberrations after disease progression or treatment administration [29]
Zborovskaya I 1999 18 samples from 9 cases PCR on microsatellite markers In 5 out of 9 cases the LOH patterns were different in the primary tumor and the metastatic nodes [33]
Fishman A 2005 14 samples from 7 cases Chromosomal comparative genomic hybridization 6 out of 7 cases presented less chromosomal aberrations or normal genomes in metastatic sites than in paired primary lesions [35]
Khalique L 2007 110 samples from 16 cases PCR on microsatellite markers, multiplex SNP analysis, maximum parsimony tree analysis All cases are monoclonal in origin and display extensive intra-tumor heterogeneity [41]
Khalique L 2009 186 samples from 22 cases PCR on microsatellite markers, maximum parsimony tree analysis Monoclonal origin but become polyclonal with different clones gaining metastatic potential during early and late stages of evolution. There is extensive heterogeneity between metastatic samples with no significant differences from primary tumor [42]
Cooke SL 2010 3 platinum sensitive and 4 platinum resistant cell lines derived from 3 patients, 6 paired pre/post neoadjuvant chemotherapy samples Array CGH, M-FISH, Array SNP Platinum resistance develops from pre-existing minor clones but no enrichment is observed after short-term chemotherapy [36]
Micci F 2010 70 samples from 32 cases Chromosomal banding, HR-CGH Metastatic spread to the contralateral ovary is a late event in evolution [31]
Ng CK 2012 2 platinum sensitive and 2 platinum resistant cell lines from 2 patients NGS Tandem duplicator mutator phenotype is an ongoing phenotype that arose early before divergence of platinum sensible/resistant lineages and might represent a novel DNA repair defect independent of HR [37]
Bashashati A 2013 29 samples from 5 cases and 2 paired temporal samples from 1 case NGS, SNP array, RNA array Extensive heterogeneity at all levels with early divergence and highly individual evolutionary trajectories. TP53 is the only consistent mutation across samples. Cell free DNA offers a narrow and heterogeneous picture of common ancestral mutations. Stable clonal population at relapse might be a feature of long survivorship [43]
Castellarin M 2013 6 paired temporal samples from 2 cases NGS 89% of mutations found in relapsed tumors are present in primary tumors. Predominant TP53 mutations in all samples [38]
Tone AA 2014 19 primary and 18 recurrent samples from 11 cases Cancer hotspot NGS Almost half of patients with low grade SOC had RAS/RAF pathway mutations. Among them, 20% exhibit spatial and temporal heterogeneity [48]
Lee JY 2015 11 samples from 1 case NGS, SNP array Early divergence of primary clusters, metastatic cluster accumulated few mutations. Only 6% shared somatic mutations across all samples except TP53 [44]
Mota A 2015 6 primary and 6 recurrent samples from 1 case NGS, CGH Significant mutational divergence, with 41% shared somatic variants between 1 primary and 2 recurrent samples [39]
Schwarz RF 2015 135 samples from 14 cases SNP array, NGS, Digital PCR, MEDICC algorithm Potentially unknown mutator phenotypes lead to non-clock-like evolutionary trajectories. There are only minor genomic changes (in comparison with the overall changes) with neoadjuvant chemotherapy, with an average of 46 new genomic events. Patients with high clonal expansion have a shorter survival. Marked early divergent evolution of relapsed samples [49]
Eckert MA 2016 32 samples from 8 patients NGS Various anatomic sites have similar mutation burden indicative of early establishment of genomic instability. STIC can represent primary or metastatic lesions [45]
Lambrechts S 2016 31 cases with paired primary and recurrent samples SNP array, NGS Huge variability between primary and recurrent tumors with 58% shared mutations between primary and recurrent samples. TP53 was the most frequently observed (18 out of 23 pairs, 78%) with few other recurrent mutations [40]
McPherson A 2016 68 samples from 7 cases NGS, Single cell sequencing Metastatic sites usually comprise oligoclonal populations with at least one polyclonal site in each patient. Two distinct modes of peritoneal spreading: monoclonal, unidirectional and polyclonal with reseeding [50]
Choi YJ 2017 25 samples and ascitic cells from 4 cases NGS, microarray CGH, methylation profiling Ascitic cancer cells diverge early through a polyseeding mechanism and accurately reflect common somatic mutations, CNAs and DNA methylations in advanced ovarian cancer [53]
Yin X 2017 22 bilateral samples from 11 cases NGS Bilateral ovarian cancer lesions have a common ancestor but diverge early and display significant heterogeneity [46]
Arend RC 2018 Paired pre/post NACT samples from 19 patients, 14 paired plasma samples NGS 50 genes, Gene expression panel Targeted sequencing of cell free DNA was not informative for NACT tumor induced changes [52]
Chien J 2018 9 samples for each of the 4 patients RNA seq Peritoneal metastases arise early and are composed of multiple subclones, with shared SNV at all regions of one patient 2.13–25% [47]
Zhang AW 2018 212 samples from 38 cases NGS, Gene expression, IHC Within patient spatial immune variation influences the dissemination of malignant clonal populations [51]