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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Artículo Open Access |
| Published: |
Wiley
2025
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| Subjects: | |
| Online Access: | https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6461 |
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Table of Contents:
- Phylogenetic analysis of paired breast carcinomas identifies genetic events associated with clonal recurrence and invasive progression Tanjina Kader Maia Zethoven Sakshi Mahale Hugo Saunders Lauren Tjoeka Rebecca Lehmann Madawa W Jayawardana Jia‐Min Pang Dorothea Lesche Neeha Rajan Timothy Semple Jue Er Amanda Lee Richard Lupat David J Byrne Siobhan Hughes Hoa Nguyen Siqi Lai Maree Pechlivanis Olivia Craig Lisa Devereux Eloise House Sureshni I Jayasinghe Tom L Kaufmann Roland F Schwarz Andrew R Green Islam M Miligy Margaret Cummings Sunil Lakhani Ian G Campbell Emad Rakha Stephen B Fox G Bruce Mann Kylie L Gorringe The Journal of Pathology Abstract Development of ipsilateral breast carcinoma following a diagnosis of breast ductal carcinoma in situ (DCIS) has been assumed to represent recurrence of the primary tumour. However, this may not always be the case, and it is important to determine how often such recurrences represent new tumours. Ipsilateral primary–recurrence pairs ( n = 78) were sequenced to test their clonal relatedness. Shared genetic events were identified from whole exome sequencing ( n = 54 pairs) using haplotype‐specific copy number and phylogenetic analysis. The remaining pairs were sequenced using a targeted panel or low‐coverage whole genome sequencing. We included 32 non‐recurrent DCIS to compare recurrent and non‐recurrent disease. We found that 7% of DCIS recurrences were non‐clonal by whole exome sequencing, indicative of a new breast carcinoma. Lower resolution methods detected a higher non‐clonality rate (29%). By comparing primary DCIS with their recurrence, we found that the evolution of DCIS to invasive disease was associated with increased ploidy and copy number events. TP53 mutations were enriched in DCIS with clonal recurrence compared with non‐recurrent DCIS. Our results verify that de novo ‘recurrent tumours’ of independent origin occur in patients who may be at high risk. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6461 http://creativecommons.org/licenses/by/4.0/