Julia Como
A5061170025- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Colorectal Cancer Screening and Detection
- Colorectal Cancer Treatments and Studies
- DNA Repair Mechanisms
- Colorectal Cancer Surgical Treatments
- BRCA gene mutations in cancer
- Helicobacter pylori-related gastroenterology studies
- RNA Research and Splicing
- Multiple and Secondary Primary Cancers
- Cancer, Lipids, and Metabolism
- Colorectal and Anal Carcinomas
- Wnt/β-catenin signaling in development and cancer
- IL-33, ST2, and ILC Pathways
- Epigenetics and DNA Methylation
- dental development and anomalies
- Inflammasome and immune disorders
Victorian Comprehensive Cancer Centre
2019-2025
The University of Melbourne
2019-2025
Hudson Institute of Medical Research
2023
Abstract Background This study aimed to investigate clinicopathological and molecular tumour features associated with intratumoral pks + Escherichia coli ( E.coli ), - (non- bacteria harbouring the island), Enterotoxigenic Bacteroides fragilis (ETBF) Fusobacterium nucleatum F. ). Methods We screened 1697 tumour-derived DNA samples from Australasian Colorectal Cancer Family Registry, Melbourne Collaborative Cohort Study ANGELS using targeted PCR. Results Pks was male sex P < 0.01) APC...
Objective Germline pathogenic variants (PVs) in the DNA mismatch repair (MMR) genes and base excision gene MUTYH underlie hereditary colorectal cancer (CRC) polyposis syndromes. We evaluated robustness discriminatory potential of tumour mutational signatures CRCs for identifying germline PV carriers. Design Whole-exome sequencing formalin-fixed paraffin-embedded (FFPE) CRC tissue was performed on 33 MMR carriers, 12 biallelic 25 sporadic MLH1 methylated MMR-deficient (MMRd controls) 160...
Abstract The interleukin-1 family members, IL-1β and IL-18, are processed into their biologically active forms by multi-protein complexes, known as inflammasomes. Although the inflammasome pathways that mediate processing in myeloid cells have been defined, those involved IL-18 processing, particularly non-myeloid cells, still not well understood. Here we report host defence molecule NOD1 regulates mouse epithelial response to mucosal pathogen, Helicobacter pylori . Specifically, mediates...
Abstract Routine screening of tumors for DNA mismatch repair (MMR) deficiency (dMMR) in colorectal (CRC), endometrial (EC) and sebaceous skin (SST) leads to a significant proportion unresolved cases classified as suspected Lynch syndrome (SLS). SLS (n = 135) were recruited from Family Cancer Clinics across Australia New Zealand. Targeted panel sequencing was performed on tumor 137; 80×CRCs, 33×ECs 24xSSTs) matched blood-derived assess microsatellite instability status, mutation burden,...
The adverse gut microbiome may underlie the variability in risks of colorectal cancer (CRC) and metachronous CRC people with Lynch syndrome (LS). role pks+/-Escherichia coli (pks+/-E. coli), Enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium nucleatum (Fn) CRCs adenomas LS is unknown. A total 358 cases, including 386 CRCs, 90 adenomas, 195 normal colonic mucosa DNA from Australasian Colon Cancer Family Registry were tested using multiplex TaqMan qPCR. Logistic regression was used to...
Abstract Approximately 30% of sebaceous skin lesions (or neoplasia) demonstrate DNA mismatch repair (MMR)-deficiency. MMR-deficiency can be caused by Lynch syndrome, resulting from germline pathogenic variants in the MMR genes MLH1 , MSH2 MSH6 and PMS2 but other causes include somatic gene promoter hypermethylation, constitutional hypermethylation ( epimutation), or biallelic mutations. In colorectal (CRCs) endometrial cancers (ECs), tumour showing loss protein expression...
Abstract Background MLH1 epimutation is characterised by constitutional monoallelic promoter hypermethylation, which can cause colorectal cancer (CRC). Tumour molecular profiles of CRCs were used to classify germline variants uncertain significance and methylated early-onset (EOCRCs). Genome-wide DNA methylation somatic mutational tumours from two : c.-11C > T one c.-[28A G; 7C T] carriers three EOCRCs (< 45 years) compared with 38 reference CRCs. Methylation-sensitive droplet digital...
Patients in whom mismatch repair (MMR)-deficient cancer develops the absence of pathogenic variants germline MMR genes or somatic hypermethylation MLH1 gene promoter are classified as having suspected Lynch syndrome (SLS). Germline whole-genome sequencing (WGS) and targeted genome-wide tumor were applied to identify underlying cause deficiency SLS. WGS was performed on samples from 14 cancer-affected patients with SLS, including two sets first-degree relatives. assessed for variants, complex...
Germline pathogenic variants in the DNA mismatch repair (MMR) genes (Lynch syndrome) predispose to colorectal (CRC) and endometrial (EC) cancer. However, mosaic MMR have been rarely described. We identified a likely de novo MSH6:c.1135_1139del p.Arg379* variant patient diagnosed with suspected Lynch syndrome/Lynch-like syndrome. The developed MSH6-deficient EC CRC at 54 58 years of age, respectively, without detectable germline variant. Multigene panel sequencing tumor blood-derived an MSH6...
Abstract Genetic susceptibility to familial colorectal cancer (CRC), including for individuals classified as Familial Colorectal Cancer Type X (FCCTX), remains poorly understood. We describe a multi-generation CRC-affected family segregating pathogenic variants in both BRCA1 , gene associated with breast and ovarian RNF43 Serrated Polyposis Syndrome (SPS). A single out of 105 families meeting the criteria FCCTX (Amsterdam I history mismatch repair (MMR)-proficient CRCs) recruited...
Routine screening of tumors for DNA mismatch repair (MMR) deficiency (dMMR) in colorectal (CRC), endometrial (EC) and sebaceous skin (SST) leads to a significant proportion unresolved cases classified as suspected Lynch syndrome (SLS). SLS (n=135) were recruited from Family Cancer Clinics across Australia New Zealand. Targeted panel sequencing was performed on tumor (n=137; 80xCRCs, 33xECs 24xSSTs) matched blood-derived assess microsatellite instability status, mutation burden, COSMIC...
<h3>Introduction/Background</h3> In PHAEDRA, a single arm Phase 2 trial (n=71), MMR deficiency (dMMR) was predictive of response to durvalumab (1500mg IV Q4W), with an objective tumour rate (OTR; defined by iRECIST) 47% in dMMR compared 3% MMR-proficient (pMMR) women advanced endometrial cancer (AEC). We investigated genomic and DNA methylation features their correlation treatment outcomes. <h3>Methodology</h3> Germline pathogenic variants genes (Lynch syndrome) or somatic gene inactivation...
ABSTRACT Background Colorectal cancers (CRCs) from people with biallelic germline likely pathogenic/pathogenic variants in MUTYH or NTHL1 exhibit specific single base substitution (SBS) mutational signatures, namely combined SBS18 and SBS36 (SBS18+SBS36), SBS30, respectively. The aim was to determine if adenomas cases demonstrated these signatures at diagnostic levels. Methods Whole-exome sequencing of FFPE tissue matched blood-derived DNA performed on 9 15 CRCs 13 cases, 7 2 5 27 26 46...
ABSTRACT Objective Germline pathogenic variants (PVs) in the DNA mismatch repair (MMR) genes and base excision gene MUTYH underlie hereditary colorectal cancer (CRC) polyposis syndromes. We evaluated robustness discriminatory potential of tumour mutational signatures CRCs for identifying germline PV carriers. Design Whole exome sequencing formalin-fixed paraffin embedded (FFPE) CRC tissue was performed on 33 MMR carriers, 12 biallelic 25 sporadic MLH1 methylated MMR-deficient (MMRd controls)...
Abstract Identifying tumor DNA mismatch repair deficiency (dMMR) is important for precision medicine. We assessed features, individually and in combination, whole-exome sequenced (WES) colorectal cancers (CRCs) panel CRCs, endometrial (ECs) sebaceous skin tumors (SSTs) their accuracy detecting dMMR. CRCs (n=300) with WES, where MMR status was determined by immunohistochemistry, were microsatellite instability (MSMuTect, MANTIS, MSIseq, MSISensor), COSMIC mutational signatures (TMS) somatic...
Abstract Background People who develop mismatch repair (MMR) deficient cancer in the absence of a germline MMR gene pathogenic variant or hypermethylation MLH1 promoter their tumor are classified as having suspected Lynch syndrome (SLS). We applied whole genome sequencing (WGS) and targeted genome-wide approaches to identify underlying cause MMR-deficiency SLS. Methods Germline WGS was performed on 14 cancer-affected people with SLS, including two sets first-degree relatives. Tumor tissue...
Abstract Germline pathogenic variants in the DNA mismatch (MMR) repair genes (Lynch syndrome) predispose to colorectal (CRC) and endometrial (EC) cancer. However, mosaic MMR have been rarely described. We identified a likely de novo MSH6 :c.1135_1139del p.Arg379* variant patient diagnosed with suspected Lynch syndrome/Lynch-like syndrome. The developed MSH6-deficient EC CRC at 54 58 years of age, respectively, without detectable germline variant. Multigene panel sequencing tumor...
5604 Background: In the single arm phase 2 PHAEDRA trial, MMR deficiency (dMMR) was predictive of response to durvalumab (1500mg IV Q4W), with an objective tumor rate (OTR; defined by iRECIST) 47% in dMMR compared 3% MMR-proficient (pMMR) advanced endometrial cancer (AEC). This substudy trial investigates molecular subtypes and other genomic features their correlation treatment outcomes. Methods: Testing performed determine dMMR, including germline pathogenic variants DNA genes (Lynch...
Abstract Germline pathogenic variants in the DNA mismatch repair (MMR) genes (Lynch syndrome) predispose to colorectal (CRC) and endometrial (EC) cancer. Lynch syndrome specific tumor features were evaluated for their ability support ACMG/InSiGHT framework classifying of uncertain clinical significance (VUS) MMR genes. Twenty-eight CRC or EC tumors from 25 VUS carriers (6x MLH1 , 9x MSH2 6x MSH6 4x PMS2 ), underwent targeted sequencing presence microsatellite instability/MMR-deficiency...
Germline pathogenic variants in the DNA mismatch repair (MMR) genes (Lynch syndrome) predispose to colorectal (CRC) and endometrial (EC) cancer. Lynch syndrome specific tumor features were evaluated for their ability support ACMG/InSiGHT framework classifying of uncertain clinical significance (VUS) MMR genes. Twenty-eight CRC or EC tumors from 25 VUS carriers (6x