A community‐based lung cancer rapid tissue donation protocol provides high‐quality drug‐resistant specimens for proteogenomic analyses
Abstract Background For the advancement of cancer research, the collection of tissue specimens from drug‐resistant tumors after targeted therapy is crucial. Although patients with lung cancer are often provided targeted therapy, post‐therapy specimens are not routinely collected due to the risks of...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.2670 |
| _version_ | 1811264590610169856 |
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| author | Theresa A. Boyle Gwendolyn P. Quinn Matthew B. Schabath Teresita Muñoz‐Antonia James J. Saller Luisa F. Duarte Laura S. Hair Jamie K. Teer Derek Y. Chiang Rebecca Leary Connie C. Wong Alexander Savchenko Angad P. Singh LaSalette Charette Kate Mendell Gullu Gorgun Scott J. Antonia Alberto A. Chiappori Benjamin C. Creelan Jhanelle E. Gray Eric B. Haura |
| author_facet | Theresa A. Boyle Gwendolyn P. Quinn Matthew B. Schabath Teresita Muñoz‐Antonia James J. Saller Luisa F. Duarte Laura S. Hair Jamie K. Teer Derek Y. Chiang Rebecca Leary Connie C. Wong Alexander Savchenko Angad P. Singh LaSalette Charette Kate Mendell Gullu Gorgun Scott J. Antonia Alberto A. Chiappori Benjamin C. Creelan Jhanelle E. Gray Eric B. Haura |
| author_sort | Theresa A. Boyle |
| collection | DOAJ |
| description | Abstract Background For the advancement of cancer research, the collection of tissue specimens from drug‐resistant tumors after targeted therapy is crucial. Although patients with lung cancer are often provided targeted therapy, post‐therapy specimens are not routinely collected due to the risks of collection, limiting the study of targeted therapy resistance mechanisms. Posthumous rapid tissue donation (RTD) is an expedient collection process that provides an opportunity to understand treatment‐resistant lung cancers. Methods Consent to participate in the thoracic RTD protocol was obtained during patient care. When death occurred, tumor and paired non‐tumor, cytology, and blood specimens were collected within 48 hours and preserved as formalin‐fixed and frozen specimens. Tissue sections were evaluated with hematoxylin and eosin staining and immunohistochemistry (IHC) against multiple biomarkers, including various programmed death ligand 1 (PD‐L1) clones. Next‐generation sequencing was performed on 13 specimens from 5 patients. Results Postmortem specimens (N = 180) were well preserved from 9 patients with lung cancer. PD‐L1 IHC revealed heterogeneity within and between tumors. An AGK‐BRAF fusion was newly identified in tumor from a donor with a known echinoderm microtubule‐associated protein‐like 4 to anaplastic lymphoma kinase (EML4‐ALK) fusion and history of anaplastic lymphoma kinase (ALK) inhibitor therapy. RNA expression analysis revealed a clonal genetic origin of metastatic cancer cells. Conclusions Post‐therapy specimens demonstrated PD‐L1 heterogeneity and an acyl glycerol kinase to B‐rapidly accelerated fibrosarcoma (AGK‐BRAF) fusion in a patient with an EML4‐ALK–positive lung adenocarcinoma as a potential resistance mechanism to ALK inhibitor therapy. Rapid tissue donation collection of postmortem tissue from lung cancer patients is a novel approach to cancer research that enables studies of molecular evolution and drug resistance. |
| first_indexed | 2024-04-12T20:07:06Z |
| format | Article |
| id | doaj.art-82ae3eb5e1ff40e2b1ca8ba0ac5ee571 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-12T20:07:06Z |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-82ae3eb5e1ff40e2b1ca8ba0ac5ee5712022-12-22T03:18:22ZengWileyCancer Medicine2045-76342020-01-019122523710.1002/cam4.2670A community‐based lung cancer rapid tissue donation protocol provides high‐quality drug‐resistant specimens for proteogenomic analysesTheresa A. Boyle0Gwendolyn P. Quinn1Matthew B. Schabath2Teresita Muñoz‐Antonia3James J. Saller4Luisa F. Duarte5Laura S. Hair6Jamie K. Teer7Derek Y. Chiang8Rebecca Leary9Connie C. Wong10Alexander Savchenko11Angad P. Singh12LaSalette Charette13Kate Mendell14Gullu Gorgun15Scott J. Antonia16Alberto A. Chiappori17Benjamin C. Creelan18Jhanelle E. Gray19Eric B. Haura20Department of Oncologic Science Morsani College of Medicine University of South Florida Tampa FL USADepartment of Ob‐Gyn New York University School of Medicine New York NY USADepartment of Oncologic Science Morsani College of Medicine University of South Florida Tampa FL USADepartment of Oncologic Science Morsani College of Medicine University of South Florida Tampa FL USAAnatomic Pathology Department H. Lee Moffitt Cancer Center & Research Institute Tampa FL USADepartment of Cancer Epidemiology H. Lee Moffitt Cancer Center & Research Institute Tampa FL USADistrict 12 Medical Examiner's Office Sarasota FL USADepartment of Oncologic Science Morsani College of Medicine University of South Florida Tampa FL USANovartis Institutes for BioMedical Research Cambridge MA USANovartis Institutes for BioMedical Research Cambridge MA USANovartis Pharmaceuticals Corporation East Hanover NJ USANovartis Pharmaceuticals Corporation East Hanover NJ USANovartis Institutes for BioMedical Research Cambridge MA USANovartis Pharmaceuticals Corporation East Hanover NJ USANovartis Pharmaceuticals Corporation East Hanover NJ USANovartis Pharmaceuticals Corporation East Hanover NJ USADepartment of Oncologic Science Morsani College of Medicine University of South Florida Tampa FL USADepartment of Oncologic Science Morsani College of Medicine University of South Florida Tampa FL USADepartment of Oncologic Science Morsani College of Medicine University of South Florida Tampa FL USADepartment of Oncologic Science Morsani College of Medicine University of South Florida Tampa FL USADepartment of Oncologic Science Morsani College of Medicine University of South Florida Tampa FL USAAbstract Background For the advancement of cancer research, the collection of tissue specimens from drug‐resistant tumors after targeted therapy is crucial. Although patients with lung cancer are often provided targeted therapy, post‐therapy specimens are not routinely collected due to the risks of collection, limiting the study of targeted therapy resistance mechanisms. Posthumous rapid tissue donation (RTD) is an expedient collection process that provides an opportunity to understand treatment‐resistant lung cancers. Methods Consent to participate in the thoracic RTD protocol was obtained during patient care. When death occurred, tumor and paired non‐tumor, cytology, and blood specimens were collected within 48 hours and preserved as formalin‐fixed and frozen specimens. Tissue sections were evaluated with hematoxylin and eosin staining and immunohistochemistry (IHC) against multiple biomarkers, including various programmed death ligand 1 (PD‐L1) clones. Next‐generation sequencing was performed on 13 specimens from 5 patients. Results Postmortem specimens (N = 180) were well preserved from 9 patients with lung cancer. PD‐L1 IHC revealed heterogeneity within and between tumors. An AGK‐BRAF fusion was newly identified in tumor from a donor with a known echinoderm microtubule‐associated protein‐like 4 to anaplastic lymphoma kinase (EML4‐ALK) fusion and history of anaplastic lymphoma kinase (ALK) inhibitor therapy. RNA expression analysis revealed a clonal genetic origin of metastatic cancer cells. Conclusions Post‐therapy specimens demonstrated PD‐L1 heterogeneity and an acyl glycerol kinase to B‐rapidly accelerated fibrosarcoma (AGK‐BRAF) fusion in a patient with an EML4‐ALK–positive lung adenocarcinoma as a potential resistance mechanism to ALK inhibitor therapy. Rapid tissue donation collection of postmortem tissue from lung cancer patients is a novel approach to cancer research that enables studies of molecular evolution and drug resistance.https://doi.org/10.1002/cam4.2670donationheterogeneitylung cancerPD‐L1rapid autopsyresistance mutation |
| spellingShingle | Theresa A. Boyle Gwendolyn P. Quinn Matthew B. Schabath Teresita Muñoz‐Antonia James J. Saller Luisa F. Duarte Laura S. Hair Jamie K. Teer Derek Y. Chiang Rebecca Leary Connie C. Wong Alexander Savchenko Angad P. Singh LaSalette Charette Kate Mendell Gullu Gorgun Scott J. Antonia Alberto A. Chiappori Benjamin C. Creelan Jhanelle E. Gray Eric B. Haura A community‐based lung cancer rapid tissue donation protocol provides high‐quality drug‐resistant specimens for proteogenomic analyses Cancer Medicine donation heterogeneity lung cancer PD‐L1 rapid autopsy resistance mutation |
| title | A community‐based lung cancer rapid tissue donation protocol provides high‐quality drug‐resistant specimens for proteogenomic analyses |
| title_full | A community‐based lung cancer rapid tissue donation protocol provides high‐quality drug‐resistant specimens for proteogenomic analyses |
| title_fullStr | A community‐based lung cancer rapid tissue donation protocol provides high‐quality drug‐resistant specimens for proteogenomic analyses |
| title_full_unstemmed | A community‐based lung cancer rapid tissue donation protocol provides high‐quality drug‐resistant specimens for proteogenomic analyses |
| title_short | A community‐based lung cancer rapid tissue donation protocol provides high‐quality drug‐resistant specimens for proteogenomic analyses |
| title_sort | community based lung cancer rapid tissue donation protocol provides high quality drug resistant specimens for proteogenomic analyses |
| topic | donation heterogeneity lung cancer PD‐L1 rapid autopsy resistance mutation |
| url | https://doi.org/10.1002/cam4.2670 |
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