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01.02.2016 | Preclinical Study

Whole exome sequencing of rare aggressive breast cancer histologies

verfasst von: Maria Vittoria Dieci, Veronika Smutná, Véronique Scott, Guangliang Yin, Ran Xu, Philippe Vielh, Marie-Christine Mathieu, Cécile Vicier, Melanie Laporte, Francoise Drusch, Valentina Guarneri, Pierfranco Conte, Suzette Delaloge, Ludovic Lacroix, Olivia Fromigué, Fabrice André, Celine Lefebvre

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2016

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Abstract

Little is known about mutational landscape of rare breast cancer (BC) subtypes. The aim of the study was to apply next generation sequencing to three different subtypes of rare BCs in order to identify new genes related to cancer progression. We performed whole exome and targeted sequencing of 29 micropapillary, 23 metaplastic, and 27 pleomorphic lobular BCs. Micropapillary BCs exhibit a profile comparable to common BCs: PIK3CA, TP53, GATA3, and MAP2K4 were the most frequently mutated genes. Metaplastic BCs presented a high frequency of TP53 (78 %) and PIK3CA (48 %) mutations and were recurrently mutated on KDM6A (13 %), a gene involved in histone demethylation. Pleomorphic lobular carcinoma exhibited high mutation rate of PIK3CA (30 %), TP53 (22 %), and CDH1 (41 %) and also presented mutations in PYGM, a gene involved in glycogen metabolism, in 8 out of 27 samples (30 %). Further analyses of publicly available datasets showed that PYGM is dramatically underexpressed in common cancers as compared to normal tissues and that low expression in tumors is correlated with poor relapse-free survival. Immunohistochemical staining on formalin-fixed paraffin-embedded tissues available in our cohort of patients confirmed higher PYGM expression in normal breast tissue compared to equivalent tumoral zone. Next generation sequencing methods applied on rare cancer subtypes can serve as a useful tool in order to uncover new potential therapeutic targets. Sequencing of pleomorphic lobular carcinoma identified a high rate of alterations in PYGM. These findings emphasize the role of glycogen metabolism in cancer progression.

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Titel: Whole exome sequencing of rare aggressive breast cancer histologies
verfasst von: Maria Vittoria Dieci
Veronika Smutná
Véronique Scott
Guangliang Yin
Ran Xu
Philippe Vielh
Marie-Christine Mathieu
Cécile Vicier
Melanie Laporte
Francoise Drusch
Valentina Guarneri
Pierfranco Conte
Suzette Delaloge
Ludovic Lacroix
Olivia Fromigué
Fabrice André
Celine Lefebvre
Publikationsdatum: 01.02.2016
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2016
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-016-3718-y

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Whole exome sequencing of rare aggressive breast cancer histologies

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