Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrences
Abstract Genomic alterations of anal squamous cell carcinoma (ASCC) remain poorly understood due to the rarity of this tumor. Array comparative genomic hybridization and targeted gene sequencing were performed in 49 cases of ASCC. The most frequently altered regions (with a frequency greater than 25...
| Published in: | Cancer Medicine |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-07-01
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| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.1533 |
| _version_ | 1850034221003833344 |
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| author | Wulfran Cacheux Petros Tsantoulis Adrien Briaux Sophie Vacher Pascale Mariani Marion Richard‐Molard Bruno Buecher Sophie Richon Emmanuelle Jeannot Julien Lazartigues Etienne Rouleau Odette Mariani Elsy El Alam Jérôme Cros Sergio Roman‐Roman Emmanuel Mitry Elodie Girard Virginie Dangles‐Marie Astrid Lièvre Ivan Bièche |
| author_facet | Wulfran Cacheux Petros Tsantoulis Adrien Briaux Sophie Vacher Pascale Mariani Marion Richard‐Molard Bruno Buecher Sophie Richon Emmanuelle Jeannot Julien Lazartigues Etienne Rouleau Odette Mariani Elsy El Alam Jérôme Cros Sergio Roman‐Roman Emmanuel Mitry Elodie Girard Virginie Dangles‐Marie Astrid Lièvre Ivan Bièche |
| author_sort | Wulfran Cacheux |
| collection | DOAJ |
| container_title | Cancer Medicine |
| description | Abstract Genomic alterations of anal squamous cell carcinoma (ASCC) remain poorly understood due to the rarity of this tumor. Array comparative genomic hybridization and targeted gene sequencing were performed in 49 cases of ASCC. The most frequently altered regions (with a frequency greater than 25%) were 10 deleted regions (2q35, 2q36.3, 3p21.2, 4p16.3, 4p31.21, 7q36.1, 8p23.3, 10q23.2, 11q22.3, and 13q14.11) and 8 gained regions (1p36.33, 1q21.1, 3q26.32, 5p15.33, 8q24.3, 9q34.3, 16p13.3, and 19p13.3). The most frequent minimal regions of deletion (55%) encompassed the 11q22.3 region containing ATM, while the most frequent minimal regions of gain (57%) encompassed the 3q26.32 region containing PIK3CA. Recurrent homozygous deletions were observed for 5 loci (ie, TGFR2 in 4 cases), and recurrent focal amplifications were observed for 8 loci (ie, DDR2 and CCND1 in 3 cases, respectively). Several of the focal amplified genes are targets for specific therapies. Integrated analysis showed that the PI3K/Akt/mTOR signaling pathway was the pathway most extensively affected, particularly in recurrences compared to treatment‐naive tumors (64% vs 30%; P = .017). In patients with ASCC recurrences, poor overall survival (OS) was significantly correlated with a large number of altered regions (P = .024). These findings provide insight into the somatic genomic alterations in ASCC and highlight the key role of the druggable PI3K/Akt/mTOR signaling pathway. |
| format | Article |
| id | doaj-art-d6a66e8ea6d94ae682fa4e09e0721f7f |
| institution | Directory of Open Access Journals |
| issn | 2045-7634 |
| language | English |
| publishDate | 2018-07-01 |
| publisher | Wiley |
| record_format | Article |
| spelling | doaj-art-d6a66e8ea6d94ae682fa4e09e0721f7f2025-08-20T00:34:50ZengWileyCancer Medicine2045-76342018-07-01773213322510.1002/cam4.1533Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrencesWulfran Cacheux0Petros Tsantoulis1Adrien Briaux2Sophie Vacher3Pascale Mariani4Marion Richard‐Molard5Bruno Buecher6Sophie Richon7Emmanuelle Jeannot8Julien Lazartigues9Etienne Rouleau10Odette Mariani11Elsy El Alam12Jérôme Cros13Sergio Roman‐Roman14Emmanuel Mitry15Elodie Girard16Virginie Dangles‐Marie17Astrid Lièvre18Ivan Bièche19Département d’oncologie médicale Institut Curie, Ensemble hospitalier Hôpital René Huguenin Saint‐Cloud FranceCentre d’oncologie Hôpitaux universitaires de Genève Genève SwitzerlandUnité de pharmacogénomique Département de génétique Institut Curie, Ensemble hospitalier Paris Cedex 05 FranceUnité de pharmacogénomique Département de génétique Institut Curie, Ensemble hospitalier Paris Cedex 05 FranceDépartement de chirurgie oncologique Institut Curie, Ensemble hospitalier Paris Cedex 05 FranceDépartement de radio‐oncologie Institut Curie, Ensemble hospitalier Hôpital René Huguenin Saint‐Cloud FranceDépartement d’oncologie médicale Institut Curie, Ensemble hospitalier Paris Cedex 05 FranceCentre de recherche Institut Curie UMR144 Paris Cedex 05 FranceDépartement d’anatomopathologie Institut Curie, Ensemble hospitalier Paris Cedex 05 FranceUnité de pharmacogénomique Département de génétique Institut Curie, Ensemble hospitalier Paris Cedex 05 FranceUnité de pharmacogénomique Département de génétique Institut Curie, Ensemble hospitalier Paris Cedex 05 FranceDépartement d’anatomopathologie Institut Curie, Ensemble hospitalier Paris Cedex 05 FranceDépartement d’anatomopathologie Institut Curie, Ensemble hospitalier Hôpital René Huguenin Saint‐Cloud FranceUnité de pharmacogénomique Département de génétique Institut Curie, Ensemble hospitalier Paris Cedex 05 FranceRecherche translationnelle Centre de recherche Institut Curie Paris Cedex 05 FranceDépartement d’oncologie médicale Institut Curie, Ensemble hospitalier Hôpital René Huguenin Saint‐Cloud FranceDépartement de bio‐informatiques Centre de recherche Institut Curie Paris Cedex 05 FranceRecherche translationnelle Centre de recherche Institut Curie Paris Cedex 05 FranceDépartement d’oncologie médicale Institut Curie, Ensemble hospitalier Hôpital René Huguenin Saint‐Cloud FranceUnité de pharmacogénomique Département de génétique Institut Curie, Ensemble hospitalier Paris Cedex 05 FranceAbstract Genomic alterations of anal squamous cell carcinoma (ASCC) remain poorly understood due to the rarity of this tumor. Array comparative genomic hybridization and targeted gene sequencing were performed in 49 cases of ASCC. The most frequently altered regions (with a frequency greater than 25%) were 10 deleted regions (2q35, 2q36.3, 3p21.2, 4p16.3, 4p31.21, 7q36.1, 8p23.3, 10q23.2, 11q22.3, and 13q14.11) and 8 gained regions (1p36.33, 1q21.1, 3q26.32, 5p15.33, 8q24.3, 9q34.3, 16p13.3, and 19p13.3). The most frequent minimal regions of deletion (55%) encompassed the 11q22.3 region containing ATM, while the most frequent minimal regions of gain (57%) encompassed the 3q26.32 region containing PIK3CA. Recurrent homozygous deletions were observed for 5 loci (ie, TGFR2 in 4 cases), and recurrent focal amplifications were observed for 8 loci (ie, DDR2 and CCND1 in 3 cases, respectively). Several of the focal amplified genes are targets for specific therapies. Integrated analysis showed that the PI3K/Akt/mTOR signaling pathway was the pathway most extensively affected, particularly in recurrences compared to treatment‐naive tumors (64% vs 30%; P = .017). In patients with ASCC recurrences, poor overall survival (OS) was significantly correlated with a large number of altered regions (P = .024). These findings provide insight into the somatic genomic alterations in ASCC and highlight the key role of the druggable PI3K/Akt/mTOR signaling pathway.https://doi.org/10.1002/cam4.1533anal squamous cell carcinomaarray comparative genomic hybridizationcopy number alterationsPI3K/Akt/mTOR signaling pathwaysomatic mutations |
| spellingShingle | Wulfran Cacheux Petros Tsantoulis Adrien Briaux Sophie Vacher Pascale Mariani Marion Richard‐Molard Bruno Buecher Sophie Richon Emmanuelle Jeannot Julien Lazartigues Etienne Rouleau Odette Mariani Elsy El Alam Jérôme Cros Sergio Roman‐Roman Emmanuel Mitry Elodie Girard Virginie Dangles‐Marie Astrid Lièvre Ivan Bièche Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrences anal squamous cell carcinoma array comparative genomic hybridization copy number alterations PI3K/Akt/mTOR signaling pathway somatic mutations |
| title | Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrences |
| title_full | Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrences |
| title_fullStr | Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrences |
| title_full_unstemmed | Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrences |
| title_short | Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrences |
| title_sort | array comparative genomic hybridization identifies high level of pi3k akt mtor pathway alterations in anal cancer recurrences |
| topic | anal squamous cell carcinoma array comparative genomic hybridization copy number alterations PI3K/Akt/mTOR signaling pathway somatic mutations |
| url | https://doi.org/10.1002/cam4.1533 |
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