TY - JOUR
T1 - Role of CDKN2C fluorescence in situ hybridization in the management of medullary thyroid carcinoma
AU - El Naofal, Maha
AU - Kim, Adriel
AU - Yon, Hui Yi
AU - Baity, Mohamed
AU - Ming, Zhao
AU - Bui-Griffith, Jacquelin
AU - Tang, Zhenya
AU - Robinson, Melissa
AU - Grubbs, Elizabeth G.
AU - Cote, Gilbert
AU - Hu, Peter
N1 - Funding Information:
We thank Dean Shirley Richmond for supporting the Project-Based Integrated Curriculum Development Initiative (PICDIn); laboratory exercises implanted in PICDIn formed the basis for this manuscript. We would also like to acknowledge the Department of Scientific Publications at MD Anderson Cancer Center for their careful review and edits of this manuscript. Th is work was supported in part by National Cancer Institute Grant P50 CA168505 (GJC and EGG).
Publisher Copyright:
© 2017 by the Association of Clinical Scientists, Inc.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Medullary thyroid carcinoma (MTC), an aggressive form of thyroid cancer, occurs sporadically in approximately 75% of MTCs. RET and RAS mutations play a role in about 40% and 15%, respectively, of sporadic MTCs and are predominant drivers in MTC pathways.These mutations are some of the most comprehensively described and screened for in MTC patients; however, in recent studies, other mutations in the CDKN2C gene (p18) have been implicated in the tumorigenesis of MTC. Comparative genomic hybridization analysis revealed that approximately 40% of sporadic MTC samples have loss of CDKN2C at chromosome 1p32 in addition to frequent losses of CDKN2D (p19) at chromosome 19p13. However, no feasible routine method had been established to detect loss of heterozygosity (LOH) of CDKN2C and CDKN2D. The aim of this study is to assess the feasibility of using Fluorescence in situ Hybridization (FISH) to screen MTC patients for CDKN2C and CDKN2D deletions. We subjected 5 formalin-fixed, paraffinembedded (FFPE) MTC samples with defined RET/RAS mutations to dual-color FISH assays to detect loss of CDKN2C and/or CDKN2D. We prepared spectrum orange probes using the bacterial artificial chromosomes RP11-779F9 for CDKN2C (p18) and RP11-177J4 for CDKN2D (p19) and prepared spectrum green control probes to the 1q25.2 and 19q11 regions (RP11-1146A3 and RP11-942P7, respectively). Nine FFPE normal thyroid tissue samples were used to establish the cutoff values for the FISH signal patterns. Of the five FFPE MTC samples, four and one yielded a positive significant result for CDKNN2C loss and CDKN2D loss, respectively.The results of a Clinical Laboratory Improvement Amendments validation with a CDKN2C/CKS1B probe set for CDKN2C (p18) loss of heterozygosity were 100% concordant with the FISH results obtained in this study.Thus, FISH is a fast and reliable diagnostic or prognostic indicator of gene loss in MTC.
AB - Medullary thyroid carcinoma (MTC), an aggressive form of thyroid cancer, occurs sporadically in approximately 75% of MTCs. RET and RAS mutations play a role in about 40% and 15%, respectively, of sporadic MTCs and are predominant drivers in MTC pathways.These mutations are some of the most comprehensively described and screened for in MTC patients; however, in recent studies, other mutations in the CDKN2C gene (p18) have been implicated in the tumorigenesis of MTC. Comparative genomic hybridization analysis revealed that approximately 40% of sporadic MTC samples have loss of CDKN2C at chromosome 1p32 in addition to frequent losses of CDKN2D (p19) at chromosome 19p13. However, no feasible routine method had been established to detect loss of heterozygosity (LOH) of CDKN2C and CDKN2D. The aim of this study is to assess the feasibility of using Fluorescence in situ Hybridization (FISH) to screen MTC patients for CDKN2C and CDKN2D deletions. We subjected 5 formalin-fixed, paraffinembedded (FFPE) MTC samples with defined RET/RAS mutations to dual-color FISH assays to detect loss of CDKN2C and/or CDKN2D. We prepared spectrum orange probes using the bacterial artificial chromosomes RP11-779F9 for CDKN2C (p18) and RP11-177J4 for CDKN2D (p19) and prepared spectrum green control probes to the 1q25.2 and 19q11 regions (RP11-1146A3 and RP11-942P7, respectively). Nine FFPE normal thyroid tissue samples were used to establish the cutoff values for the FISH signal patterns. Of the five FFPE MTC samples, four and one yielded a positive significant result for CDKNN2C loss and CDKN2D loss, respectively.The results of a Clinical Laboratory Improvement Amendments validation with a CDKN2C/CKS1B probe set for CDKN2C (p18) loss of heterozygosity were 100% concordant with the FISH results obtained in this study.Thus, FISH is a fast and reliable diagnostic or prognostic indicator of gene loss in MTC.
KW - FISH
KW - MTC
KW - RAS
KW - RET
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M3 - Article
C2 - 29066476
AN - SCOPUS:85032036719
SN - 0091-7370
VL - 47
SP - 523
EP - 528
JO - Annals of clinical and laboratory science
JF - Annals of clinical and laboratory science
IS - 5
ER -