Microfluidic chips for detecting the t(4;14) translocation and monitoring disease during treatment using reverse transcriptase-polymerase chain reaction analysis of IgH-MMSET hybrid transcripts.
Diagnosis platforms incorporating low-cost microfluidic chips enable sensitive, rapid, and accurate genetic analysis that could facilitate customized therapies tailored to match the vulnerabilities of any types of cancer. Using ex vivo cancer cells, we have detected the unique molecular signature and a chromosomal translocation in multiple myeloma. Multiple myeloma is characterized by IgH rearrangements and translocations that enable unequivocal identification of malignant cells, detected here with integrated microfluidic chips incorporating genetic amplification via reverse transcriptase-polymerase chain reaction and capillary electrophoresis. On microfluidic chips, we demonstrated accurate and versatile detection of molecular signatures in individual cancer cells, with value for monitoring response to therapy, detecting residual cancer cells that mediate relapse, and evaluating prognosis. Thus, testing for two clinically important molecular biomarkers, the IgH VDJ signature and hybrid transcripts signaling the t(4;14) chro-mosomal translocation, with predictive value in diagnosis, treatment decisions, and monitoring has been efficiently implemented on a miniaturized microfluidic system.
VanDijken
Jaron
J
Department of Oncology and Cross Cancer Institute, Edmonton, AB T6G1Z2, Canada.
Kaigala
Govind V
GV
Lauzon
Jana
J
Atrazhev
Alexey
A
Adamia
Sophia
S
Taylor
Brian J
BJ
Reiman
Tony
T
Belch
Andrew R
AR
Backhouse
Christopher J
CJ
Pilarski
Linda M
LM
D000465:Algorithms; D001853:Bone Marrow / Q000378:metabolism; D002883:Chromosomes, Human, Pair 14; D002894:Chromosomes, Human, Pair 4; D018450:Disease Progression; D020869:Gene Expression Profiling / Q000379:methods; D050438:Genes, Immunoglobulin Heavy Chain; D052138:Genes, Neoplasm; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D008991:Monitoring, Physiologic / Q000379:methods; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D014178:Translocation, Genetic
C115494:IgH-MMSET fusion protein, human; D015514:Oncogene Proteins, Fusion