title: Next-generation biobanking of metastases to enable multidimensional molecular profiling in personalized medicine.
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.
authors.affiliation: Quebec Clinical Research Organization in Cancer, Montreal, QC, Canada.
authors.forename: Zuanel
authors.initials: Z
authors.lastname: Diaz
authors.forename: Adriana
authors.initials: A
authors.lastname: Aguilar-Mahecha
authors.forename: Eric R
authors.initials: ER
authors.lastname: Paquet
authors.forename: Mark
authors.initials: M
authors.lastname: Basik
authors.forename: Michèle
authors.initials: M
authors.lastname: Orain
authors.forename: Errol
authors.initials: E
authors.lastname: Camlioglu
authors.forename: André
authors.initials: A
authors.lastname: Constantin
authors.forename: Naciba
authors.initials: N
authors.lastname: Benlimame
authors.forename: Dimcho
authors.initials: D
authors.lastname: Bachvarov
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jannot
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Simard
authors.forename: Benoit
authors.initials: B
authors.lastname: Chabot
authors.forename: Adrian
authors.initials: A
authors.lastname: Gologan
authors.forename: Roscoe
authors.initials: R
authors.lastname: Klinck
authors.forename: Thérèse
authors.initials: T
authors.lastname: Gagnon-Kugler
authors.forename: Bernard
authors.initials: B
authors.lastname: Lespérance
authors.forename: Benoit
authors.initials: B
authors.lastname: Samson
authors.forename: Petr
authors.initials: P
authors.lastname: Kavan
authors.forename: Thierry
authors.initials: T
authors.lastname: Alcindor
authors.forename: Richard
authors.initials: R
authors.lastname: Dalfen
authors.forename: Cathy
authors.initials: C
authors.lastname: Lan
authors.forename: Catherine
authors.initials: C
authors.lastname: Chabot
authors.forename: Marguerite
authors.initials: M
authors.lastname: Buchanan
authors.forename: Ewa
authors.initials: E
authors.lastname: Przybytkowski
authors.forename: Samia
authors.initials: S
authors.lastname: Qureshi
authors.forename: Caroline
authors.initials: C
authors.lastname: Rousseau
authors.forename: Alan
authors.initials: A
authors.lastname: Spatz
authors.forename: Bernard
authors.initials: B
authors.lastname: Têtu
authors.forename: Gerald
authors.initials: G
authors.lastname: Batist
mesh_terms: D017398:Alternative Splicing; D014408:Biomarkers, Tumor / Q000235:genetics*; D062005:Biopsy, Large-Core Needle; D002170:Canada; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D055028:Comparative Genomic Hybridization; D019175:DNA Methylation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary*; D035683:MicroRNAs / Q000032:analysis; D020411:Oligonucleotide Array Sequence Analysis; D018579:Patient Selection; D010641:Phenotype; D057285:Precision Medicine / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D013048:Specimen Handling; D014015:Tissue Banks; D057188:Workflow
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs