Mutational landscape of inflammatory breast cancer
Abstract Background Inflammatory breast cancer (IBC) is the most pro-metastatic form of BC. Better understanding of its enigmatic pathophysiology is crucial. We report here the largest whole-exome sequencing (WES) study of clinical IBC samples. Methods We retrospectively applied WES to 54 untreated...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-024-05198-4 |
| _version_ | 1797199219679821824 |
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| author | François Bertucci Florence Lerebours Michele Ceccarelli Arnaud Guille Najeeb Syed Pascal Finetti José Adélaïde Steven Van Laere Anthony Goncalves Patrice Viens Daniel Birnbaum Emilie Mamessier Céline Callens Davide Bedognetti |
| author_facet | François Bertucci Florence Lerebours Michele Ceccarelli Arnaud Guille Najeeb Syed Pascal Finetti José Adélaïde Steven Van Laere Anthony Goncalves Patrice Viens Daniel Birnbaum Emilie Mamessier Céline Callens Davide Bedognetti |
| author_sort | François Bertucci |
| collection | DOAJ |
| description | Abstract Background Inflammatory breast cancer (IBC) is the most pro-metastatic form of BC. Better understanding of its enigmatic pathophysiology is crucial. We report here the largest whole-exome sequencing (WES) study of clinical IBC samples. Methods We retrospectively applied WES to 54 untreated IBC primary tumor samples and matched normal DNA. The comparator samples were 102 stage-matched non-IBC samples from TCGA. We compared the somatic mutational profiles, spectra and signatures, copy number alterations (CNAs), HRD and heterogeneity scores, and frequencies of actionable genomic alterations (AGAs) between IBCs and non-IBCs. The comparisons were adjusted for the molecular subtypes. Results The number of somatic mutations, TMB, and mutational spectra were not different between IBCs and non-IBCs, and no gene was differentially mutated or showed differential frequency of CNAs. Among the COSMIC signatures, only the age-related signature was more frequent in non-IBCs than in IBCs. We also identified in IBCs two new mutational signatures not associated with any environmental exposure, one of them having been previously related to HIF pathway activation. Overall, the HRD score was not different between both groups, but was higher in TN IBCs than TN non-IBCs. IBCs were less frequently classified as heterogeneous according to heterogeneity H-index than non-IBCs (21% vs 33%), and clonal mutations were more frequent and subclonal mutations less frequent in IBCs. More than 50% of patients with IBC harbored at least one high-level of evidence (LOE) AGA (OncoKB LOE 1–2, ESCAT LOE I–II), similarly to patients with non-IBC. Conclusions We provide the largest mutational landscape of IBC. Only a few subtle differences were identified with non-IBCs. The most clinically relevant one was the higher HRD score in TN IBCs than in TN non-IBCs, whereas the most intriguing one was the smaller intratumor heterogeneity of IBCs. |
| first_indexed | 2024-04-24T07:12:17Z |
| format | Article |
| id | doaj.art-d411209f682649f3b4011eb089a7cbba |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-24T07:12:17Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-d411209f682649f3b4011eb089a7cbba2024-04-21T11:28:28ZengBMCJournal of Translational Medicine1479-58762024-04-0122111210.1186/s12967-024-05198-4Mutational landscape of inflammatory breast cancerFrançois Bertucci0Florence Lerebours1Michele Ceccarelli2Arnaud Guille3Najeeb Syed4Pascal Finetti5José Adélaïde6Steven Van Laere7Anthony Goncalves8Patrice Viens9Daniel Birnbaum10Emilie Mamessier11Céline Callens12Davide Bedognetti13Département d’Oncologie Médicale, Predictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS UMR7258, Institut Paoli-Calmettes, Aix-Marseille UniversitéDepartment of Medical Oncology, Institut Curie Saint-CloudSylvester Comprehensive Cancer Center, University of MiamiDépartement d’Oncologie Médicale, Predictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS UMR7258, Institut Paoli-Calmettes, Aix-Marseille UniversitéCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of AntwerpDépartement d’Oncologie Médicale, Predictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS UMR7258, Institut Paoli-Calmettes, Aix-Marseille UniversitéDépartement d’Oncologie Médicale, Predictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS UMR7258, Institut Paoli-Calmettes, Aix-Marseille UniversitéCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of AntwerpDepartment of Medical Oncology, Institut Paoli-Calmettes, Aix-Marseille UniversitéDepartment of Medical Oncology, Institut Paoli-Calmettes, Aix-Marseille UniversitéDépartement d’Oncologie Médicale, Predictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS UMR7258, Institut Paoli-Calmettes, Aix-Marseille UniversitéDépartement d’Oncologie Médicale, Predictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS UMR7258, Institut Paoli-Calmettes, Aix-Marseille UniversitéDepartment of Medical Oncology, Institut Curie Saint-CloudTumor Biology and Immunology Laboratory, Research Branch, Sidra MedicineAbstract Background Inflammatory breast cancer (IBC) is the most pro-metastatic form of BC. Better understanding of its enigmatic pathophysiology is crucial. We report here the largest whole-exome sequencing (WES) study of clinical IBC samples. Methods We retrospectively applied WES to 54 untreated IBC primary tumor samples and matched normal DNA. The comparator samples were 102 stage-matched non-IBC samples from TCGA. We compared the somatic mutational profiles, spectra and signatures, copy number alterations (CNAs), HRD and heterogeneity scores, and frequencies of actionable genomic alterations (AGAs) between IBCs and non-IBCs. The comparisons were adjusted for the molecular subtypes. Results The number of somatic mutations, TMB, and mutational spectra were not different between IBCs and non-IBCs, and no gene was differentially mutated or showed differential frequency of CNAs. Among the COSMIC signatures, only the age-related signature was more frequent in non-IBCs than in IBCs. We also identified in IBCs two new mutational signatures not associated with any environmental exposure, one of them having been previously related to HIF pathway activation. Overall, the HRD score was not different between both groups, but was higher in TN IBCs than TN non-IBCs. IBCs were less frequently classified as heterogeneous according to heterogeneity H-index than non-IBCs (21% vs 33%), and clonal mutations were more frequent and subclonal mutations less frequent in IBCs. More than 50% of patients with IBC harbored at least one high-level of evidence (LOE) AGA (OncoKB LOE 1–2, ESCAT LOE I–II), similarly to patients with non-IBC. Conclusions We provide the largest mutational landscape of IBC. Only a few subtle differences were identified with non-IBCs. The most clinically relevant one was the higher HRD score in TN IBCs than in TN non-IBCs, whereas the most intriguing one was the smaller intratumor heterogeneity of IBCs.https://doi.org/10.1186/s12967-024-05198-4Inflammatory breast cancerCopy number alterationMutationWhole-exome sequencing |
| spellingShingle | François Bertucci Florence Lerebours Michele Ceccarelli Arnaud Guille Najeeb Syed Pascal Finetti José Adélaïde Steven Van Laere Anthony Goncalves Patrice Viens Daniel Birnbaum Emilie Mamessier Céline Callens Davide Bedognetti Mutational landscape of inflammatory breast cancer Journal of Translational Medicine Inflammatory breast cancer Copy number alteration Mutation Whole-exome sequencing |
| title | Mutational landscape of inflammatory breast cancer |
| title_full | Mutational landscape of inflammatory breast cancer |
| title_fullStr | Mutational landscape of inflammatory breast cancer |
| title_full_unstemmed | Mutational landscape of inflammatory breast cancer |
| title_short | Mutational landscape of inflammatory breast cancer |
| title_sort | mutational landscape of inflammatory breast cancer |
| topic | Inflammatory breast cancer Copy number alteration Mutation Whole-exome sequencing |
| url | https://doi.org/10.1186/s12967-024-05198-4 |
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