Next-generation biobanking of metastases to enable multidimensional molecular profiling in personalized medicine.
Mod Pathol
; 26(11): 1413-24, 2013 Nov.
Article
en En
| MEDLINE
| ID: mdl-23743930
ABSTRACT
Great advances in analytical technology coupled with accelerated new drug development and growing understanding of biological challenges, such as tumor heterogeneity, have required a change in the focus for biobanking. Most current banks contain samples of primary tumors, but linking molecular signatures to therapeutic questions requires serial biopsies in the setting of metastatic disease, next-generation of biobanking. Furthermore, an integration of multidimensional analysis of various molecular components, that is, RNA, DNA, methylome, microRNAome and post-translational modifications of the proteome, is necessary for a comprehensive view of a tumor's biology. While data using such biopsies are now regularly presented, the preanalytical variables in tissue procurement and processing in multicenter studies are seldom detailed and therefore are difficult to duplicate or standardize across sites and across studies. In the context of a biopsy-driven clinical trial, we generated a detailed protocol that includes morphological evaluation and isolation of high-quality nucleic acids from small needle core biopsies obtained from liver metastases. The protocol supports stable shipping of samples to a central laboratory, where biopsies are subsequently embedded in support media. Designated pathologists must evaluate all biopsies for tumor content and macrodissection can be performed if necessary to meet our criteria of >60% neoplastic cells and <20% necrosis for genomic isolation. We validated our protocol in 40 patients who participated in a biopsy-driven study of therapeutic resistance in metastatic colorectal cancer. To ensure that our protocol was compatible with multiplex discovery platforms and that no component of the processing interfered with downstream enzymatic reactions, we performed array comparative genomic hybridization, methylation profiling, microRNA profiling, splicing variant analysis and gene expression profiling using genomic material isolated from liver biopsy cores. Our standard operating procedures for next-generation biobanking can be applied widely in multiple settings, including multicentered and international biopsy-driven trials.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Bancos de Tejidos
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Neoplasias Colorrectales
/
Biomarcadores de Tumor
/
Pruebas Genéticas
/
Medicina de Precisión
/
Neoplasias Hepáticas
Tipo de estudio:
Clinical_trials
/
Guideline
/
Prognostic_studies
Límite:
Humans
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Mod Pathol
Asunto de la revista:
PATOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Canadá