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Case 3. No. 017. High Grade PIN does not display Loss of Heterozygosity (LOH) at the mutation locus in BRCA2 mutation carriers with aggressive prostate cancer. Willems -Jones, AJ. 1 , Liam Kavanagh 1,2 , Thorne, HJ. 1 , Fox S. 3 , Clouston D. 4 and Bolton DM. 2 .

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Case 3

No. 017

High Grade PIN does not display Loss of Heterozygosity (LOH) at the mutation locus in BRCA2 mutation carriers with aggressive prostate cancer

Willems-Jones, AJ. 1, Liam Kavanagh1,2, Thorne, HJ. 1, Fox S. 3, Clouston D. 4 and Bolton DM. 2.

Urology Research Fellow, Austin Health & Peter MacCallum Centre

1. kConFab, Peter MacCallum Cancer Centre 2. Dept. Urology, Austin health 3. Dept. Pathology, Peter MacCallum Cancer Centre 4. Focus Pathology

Introduction

The risk of developing prostate cancer is increased for men carrying a pathogenic germline mutation in BRCA2. 1,2

High-grade prostatic intraepithelial neoplasia (HG PIN) has been considered a precursor to prostate adenocarcinoma. 3

Results

This sequencing chromatogram, shows our third case, with the arrow highlighting the site of the BRCA2 mutation. The two different peaks demonstrate NO loss of heterozygosity, i.e. the normal allele remains intact.

Within this small cohort of 10 pathogenic BRCA2 mutation carriers, no participant displayed loss of heterozygosity at the mutation locus within HG PIN, irrespective of whether or not the invasive tumour DNA displayed LOH.

These findings suggest that HG PIN is not a precursor to tumour development in this group of BRCA2 mutation carriers.

Aim

The aim of this study is to determine if HG PIN displays genetic hallmarks identifying it as a precursor of tumour development and progression in this group of men.

Methods

Using the kConFab tissue bank, we retrieved 10 prostatectomy specimens from men with a positive BRCA2 carrier status.

A uro-pathologist then marked out areas of normal tissue, PIN tissue & invasive tissue.

Using our ‘laser’ capture microscope, we microdissected HGPIN tissue from these cresyl-violet stained slides, & then extracted the DNA from these HGPIN samples.

The final step involved PCR of these DNA samples, examining the mutation site for loss of heterozygosity (LOH).

Conclusions

Please direct any queries to the Program Manager:

07 3354 4629program@urologymeeting.com.au

References

1. Gallagher, D. J., et al. (2010). Clinical Cancer Research16(7): 2115.

2. Thorne, H., Willems, A. J. et al. (2011). Cancer Prevention Research 4(7): 1002.

3. Schlesinger, C., D. G. Bostwick, et al. (2005). American Journal of Surgical Pathology29(9): 1201.

.

Acknowledgements

Ms Heather Thorne, kConFab, Peter MacCallum Centre; A/Prof Damien Bolton, Austin Hospital, University of Melbourne; Dr David Clouston, Focus Pathology;

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