HBOC-VUS WORKSHOP | June 28-30, 2022
Golden Tulip Leiden Centre, Schipholweg 3, 2316 XB Leiden, the Netherlands
Functional Analysis of Sequence Variants in
Hereditary Breast and Ovarian Cancer Genes
Future perspective on variant classification in cancer risk prediction and precision oncology
The VUS workshop is aimed to bring together an outstanding and diverse group of clinicians and scientists to cover the most up-to-date advances in the field of Variants of Uncertain Significance (VUS) in Hereditary Breast and Ovarian Cancer (HBOC). Topics will include clinical utility and future perspective of HBOC genes, (high throughput) functional analysis of variants in HBOC genes, mechanisms of tumorigenesis related to HBOC genes, identification of tumor vulnerabilities, predicting therapy response and synthetic lethality and resistance mechanisms related to therapy.
Organizers: Haico van Attikum, Maaike Vreeswijk, Jos Jonkers, Arne N. Kousholt, Peter Bouwman
The deadline for registration is passed.
Registration fee:
€ 275 which includes lunch, snacks, drinks and dinners as indicated in the program.
Final Program
Day 1 – Tuesday June 28
14:00 – 14:15
Welcome
14.15 – 17.35
SESSION 1: HBOC genes, current status, clinical utility and future perspective
Chair: Maaike Vreeswijk
14:15 – 14:45
Doug Easton | Breast and ovarian cancer susceptibility genes
14:45 – 15:10
Mandy Spurdle | Variant classification approaches
15:10 – 15:35
Arjen Mensenkamp | The Dutch CRAFT experience – implementation of functional tests in clinical diagnostics
15:35 – 16:00
Clare Turnbull | CanVIG-UK: an inter-disciplinary national network for improving variant classification
16:00-16:30 Tea break
16:30 – 16:55
Diana Eccles | Clinical utility of current knowledge
16:55 – 17:15
Jan Hauke* | Integrating bioinformatics and functional genomics in the clinical classification of genetic variation: Hereditary breast and ovarian cancer as a paradigm (HerediVar)
17:15 – 17:35
Shridar Ganesan* | Inferring germline and allelic status of DNA repair genes in clinical-grade tumor sequencing data
* Selected abstracts
17.35 - 19.00
Poster session I – drinks
19.30
Dinner (Grand Café de Burcht, Burgsteeg 14, 2312 JS Leiden)
Day 2 – Wednesday June 29
09.00 – 17:00
SESSION 2: Functional analysis of variants
Chairs: Peter Bouwman and Jos Jonkers
9:00 – 9:25
Fergus Couch | Comprehensive functional and clinical characterization identifies a hotspot of inactivating missense variants in RAD51C
9:25 – 9:50
Arne Nedergaard | BRIP1 C-terminal frameshift or nonsense gene variants are likely benign
9:50 – 10:15
Zdenek Kleibl | Functional analysis of CHEK2
10:15 – 10:35
Rick Boonen* | Functional characterization of PALB2 variants affecting RNA splicing
10:35-11:05 Coffee break
11:05 – 11:30
Greg Findlay | Saturation Genome Editing of BRCA1
11:30 – 11:55
Haico van Attikum | High-throughput analysis of PALB2 missense variants: linking functional impact to breast cancer risk
11:55 – 12:15
Aura Carreira* | Contributing to cancer risk assessment through the characterization of BRCA2 missense VUS’s impact on function
12:15 – 12:35
Alex Zelensky* | Segmental BRCAness induced by cancer testis antigen HSF2BP
12:35-13:45 Lunch
13:45 – 14:10
Fritz Roth | A missense variant effect map for the CHEK2 tumour suppressor
14:10 – 14:35
Evgueni Ivakine | Analysis of BRCA2 variants via saturation prime editing
14:35 – 15:00
Claus Sørensen | Fast and quantitative approach for precision functional analysis of HBOC genetic variants
15:00 – 15:20
Emilia Pulver* | MYC expression promotes hormone-independent mammary lobuloalveolar formation and tumorigenesis in male triple-negative breast cancer mice
15:20-15:45 Coffee break
15:45-17:00
Discuss future of variant classification; Towards the clinical implementation of functional data into clinical decision making
* Selected abstracts
17.00 - 18.30
Poster session II – drinks
19.00
Dinner (Brasserie de Poort, Haven 100, 2312 ML Leiden)
Day 3 – Thursday June 30
09.00 – 11.30
SESSION 3: Mechanisms of tumorigenesis related to HBOC genes
Chair: Haico van Attikum
9:00 – 9:25
Jo Morris | What underlies the synthetic lethality between BRCA1/2 loss and Polymerase Theta inhibition
9:25 – 9:50
Marcel van Vugt | PARP inhibition: cellular responses and biomarkers of efficacy
9:50 – 10:15
Alex Sartori | Defining the CtIP C-terminal domain as a critical module in genome maintenance
10:15 – 10:40
Bing Xia | Mechanisms of PALB2-associated tumorigenesis
10:40 – 11:05 Coffee break
11:05 – 11:30
Alan D’Andrea | CHAMP1 binds to REV7/FANCV and Promotes Homologous Recombination Repair
11.30 - 15:45
SESSION 4: Identification of tumor vulnerabilities, predicting therapy response
Chair: Arne Nedergaard
11:30 – 11:55
Helen Davies | Mutational signatures of HR deficiency
11:55 – 12:20
Susan Domchek | Targeted therapies for DNA damage repair
12:20 – 12:45
Jos Jonkers | Understanding and overcoming resistance to PARP inhibitors in cancer therapy
12:45-13:45 Lunch
13:45 – 14:10
Alba Llop-Guevara | RAD51 as a functional biomarker of HR deficiency
14:10 – 14:35
Edwin Cuppen | Pan-cancer mutational characteristics and HR deficiency
14:35 – 14:55
Intidhar Labidi-Galy* | Association of location of BRCA1 and BRCA2 mutations with benefit from olaparib and bevacizumab maintenance in high-grade ovarian cancer: Phase III PAOLA-1/ENGOT-ov25 trial subgroup exploratory analysis
14:55 – 15:15
Andrew Blackford* | Loss of the Bloom syndrome helicase BLM is synthetic lethal with BRCA1 deficiency
15:15-15:45 Coffee break
* Selected abstracts
15.45 – 18.45
SESSION 5: Synthetic lethality and resistance mechanisms related to therapy
Chair: Haico van Attikum
15:45 – 16:10
Arnab Ray Chaudhuri | Modulating replication stress response as a vulnerability to target BRCA2 deficient tumors
16:10 – 16:35
Ross Chapman | Dissecting mutational DNA repair processes in BRCA1 mutant cancers
16:35 – 17:00
Sharon Cantor | Addressing the Replication Gap in Cancer
17:00-17:30 Drinks
17:30 – 17:55
Bert van de Kooij | Specific killing of BRCA1-deficient cancer cells by depletion of EXO1
17:55 – 18:20
Raphel Ceccaldi | Studying new vulnerabilities in PARP inhibitor resistant, BRCA-mutated tumors
18:20 – 18:45
Sven Rottenberg | MDC1 counteracts restrained replication fork restart and its loss causes PARP inhibitor resistance in BRCA1/2-deficient mammary tumors