A community‐based lung cancer rapid tissue donation protocol provides high‐quality drug‐resistant specimens for proteogenomic analyses

Autor: Gwendolyn P. Quinn, Alexander Savchenko, Scott J. Antonia, Jamie K. Teer, Matthew B. Schabath, Teresita Muñoz-Antonia, Kate Mendell, Rebecca Leary, Gullu Gorgun, Alberto Chiappori, Jhanelle E. Gray, Laura S Hair, Benjamin C. Creelan, Derek Y. Chiang, James Saller, LaSalette Charette, Eric B. Haura, Wong Connie C, Luisa F. Duarte, Angad P Singh, Theresa A. Boyle
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Cancer Research
Pathology
Lung Neoplasms
Oncogene Proteins
Fusion
medicine.medical_treatment
H&E stain
resistance mutation
B7-H1 Antigen
Targeted therapy
0302 clinical medicine
Anaplastic lymphoma kinase
Medicine
Lung
Original Research
donation
High-Throughput Nucleotide Sequencing
Middle Aged
specimen quality
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Immunohistochemistry
3. Good health
Phosphotransferases (Alcohol Group Acceptor)
Oncology
030220 oncology & carcinogenesis
Florida
Adenocarcinoma
Female
Proto-Oncogene Proteins B-raf
medicine.medical_specialty
Community-Based Participatory Research
Tissue and Organ Procurement
medicine.drug_class
Adenocarcinoma of Lung
lcsh:RC254-282
Evolution
Molecular
03 medical and health sciences
Genetic Heterogeneity
Tissue Donation
rapid autopsy
Biomarkers
Tumor
Humans
Radiology
Nuclear Medicine and imaging
Lung cancer
Aged
business.industry
Clinical Cancer Research
medicine.disease
ALK inhibitor
lung cancer
030104 developmental biology
Drug Resistance
Neoplasm
PD‐L1
heterogeneity
business
Zdroj: Cancer Medicine, Vol 9, Iss 1, Pp 225-237 (2020)
Cancer Medicine
ISSN: 2045-7634
Popis: 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.
We collected high‐quality primary and metastatic lung cancer specimens from donors after death by rapid collection in the community. Protein analysis of this tissue revealed discordant programmed death ligand 1 (PD‐L1) results at different cancer sites from the same patient; genetic analysis identified anaplastic lymphoma kinase (ALK) and B‐rapidly accelerated fibrosarcoma (BRAF) gene fusions in a patient with a history of ALK inhibitor therapy and a clonal genetic origin of metastatic cancer cells.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje