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Reference

Exomic Sequencing of Medullary Thyroid Cancer Reveals Dominant and Mutually Exclusive Oncogenic Mutations in RET and RAS.

Paper Id
COSP30575
Authors
Agrawal N,Jiao Y,Sausen M,Leary R,Bettegowda C,Roberts NJ,Bhan S,Ho AS,Khan Z,Bishop J,Westra WH,Wood LD,Hruban RH,Tufano RP,Robinson B,Dralle H,Toledo SP,Toledo RA,Morris LG,Ghossein RA,Fagin JA,Chan TA,Velculescu VE,Vogelstein B,Kinzler KW,Papadopoulos N,Nelkin BD and Ball DW
Affiliation
Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Baltimore, Maryland 21287, USA. nagrawal@jhmi.edu
Journal
The Journal of clinical endocrinology and metabolism 2013;98(2):E364-9
ISSN:1945-7197
PUBMED:23264394
Abstract
Context: Medullary thyroid cancer (MTC) is a rare thyroid cancer that can occur sporadically or as part of a hereditary syndrome. Objective: To explore the genetic origin of MTC, we sequenced the protein coding exons of approximately 21,000 genes in 17 sporadic MTCs.We sequenced the exomes of 17 sporadic MTCs and validated the frequency of all recurrently mutated genes and other genes of interest in an independent cohort of 40 MTCs comprised of both sporadic and hereditary MTC.Results: We discovered 305 high-confidence mutations in the 17 sporadic MTCs in the discovery phase, or approximately 17.9 somatic mutations per tumor. Mutations in RET, HRAS, and KRAS genes were identified as the principal driver mutations in MTC. All of the other additional somatic mutations, including mutations in spliceosome and DNA repair pathways, were not recurrent in additional tumors. Tumors without RET, HRAS, or KRAS mutations appeared to have significantly fewer mutations overall in protein coding exons.Conclusions: Approximately 90% of MTCs had mutually exclusive mutations in RET, HRAS, and KRAS, suggesting that RET and RAS are the predominant driver pathways in MTC. Relatively few mutations overall and no commonly recurrent driver mutations other than RET, HRAS, and KRAS were seen in the MTC exome.
Paper Status
Curated
Genes Analysed
347
Mutated Samples
36
Total No. of Samples
36
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Genes Samples CDS Mutation AA Mutation
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Non-Mutant Genes Gene Id (COSG)
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Non-Mutant Samples Sample Id (COSS)
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Sample Name Mutation Count
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Sample ID Sample Name ID NCV Annotation Zygosity Chromosome Genome start Genome stop Genome version Strand WT seq Mut seq
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Table Information

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The table currently shows only high value (numeric) copy number data. Copy number segments are excluded if the total copy number and minor allele values are unknown.

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Sample Gene Expression Expr Level (Z-Score)

Over Expressed; Z-Score > 2.0

Under Expressed; Z-Score < -2.0

Normal; Z-Score within the range -2.0 to 2.0

CN Type Minor Allele Copy Number CN Segment Posn. Average Ploidy

1. N/A represents cases where the average ploidy value is not available( mostly ICGC samples). For some TCGA samples where the minor allele information is not available the average ploidy value could not be calculated.

2. For TCGA samples, the ASCAT algorithm was used to calculate the average ploidy.

3. For CGP samples, the PICNIC algorithm was used to calculate the average ploidy.

CNV
This tab shows the fusion mutations observed in this sample [more details]
Gene Sample Name Id Sample(COSS) CDS Mutation Somatic status Zygosity Validated Type