Uncommon mutation, but common amplifications, of the PIK3CA gene in thyroid tumors

Guojun Wu, Elizabeth Mambo, Zhongmin Guo, Shuiying Hu, Xin Huang, Susanne M. Gollin, Barry Trink, Paul W Ladenson, David Sidransky, Michael Mingzhao Xing

Research output: Contribution to journalArticle

Abstract

Context: As in many other human cancers, overactivation of the phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway occurs frequently in thyroid cancer, but the mechanism is not completely clear. Objective: Because activating mutations and genomic amplification of the PIK3CA gene, which encodes the p110a catalytic subunit of PI3K, are common in many cancers, we sought to investigate this phenomenon in thyroid tumors. Design: To search for PIK3CA mutations, we isolated genomic DNA from primary thyroid tumors of various types and performed direct sequencing of the exons of PIK3CA gene that carry the most common mutations in other cancers. We used real-time quantitative PCR to investigate genomic amplification of the PIK3CA gene. Results: We found no PIK3CA gene mutations in 37 benign thyroid adenomas, 52 papillary thyroid cancers, 25 follicular thyroid cancers, 13 anaplastic thyroid cancers, 13 medullary thyroid cancers, and seven thyroid tumor cell lines. We found a C3075T single-nucleotide polymorphism in exon 20 of this gene in two cases. With a copy number of 4 or more defined as amplification, we found PIK3CA gene amplification in four of 34 (12%) benign thyroid adenomas, three of 59 (5%) papillary thyroid cancer, five of 21 (24%) follicular thyroid cancer, none of 14 (0%) medullary thyroid cancer, and five of seven (71%) thyroid tumor cell lines. The PIK3CA gene amplification and consequent Akt activation were confirmed by fluorescence in situ hybridization and Western blotting studies using cell lines, respectively. Conclusion: These data suggest that mutation of the PIK3CA gene is not common, but its amplification is relatively common and may be a novel mechanism in activating the PI3K/Akt pathway in some thyroid tumors.

Original languageEnglish (US)
Pages (from-to)4688-4693
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number8
DOIs
StatePublished - Aug 2005

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Gene Amplification
Amplification
Tumors
Thyroid Gland
Genes
Thyroid Neoplasms
Mutation
Neoplasms
Phosphotransferases
Cells
Tumor Cell Line
Exons
Polymorphism
Fluorescence In Situ Hybridization
Single Nucleotide Polymorphism
Real-Time Polymerase Chain Reaction
Catalytic Domain
Nucleotides
Western Blotting
Fluorescence

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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Uncommon mutation, but common amplifications, of the PIK3CA gene in thyroid tumors. / Wu, Guojun; Mambo, Elizabeth; Guo, Zhongmin; Hu, Shuiying; Huang, Xin; Gollin, Susanne M.; Trink, Barry; Ladenson, Paul W; Sidransky, David; Xing, Michael Mingzhao.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 8, 08.2005, p. 4688-4693.

Research output: Contribution to journalArticle

Wu, Guojun ; Mambo, Elizabeth ; Guo, Zhongmin ; Hu, Shuiying ; Huang, Xin ; Gollin, Susanne M. ; Trink, Barry ; Ladenson, Paul W ; Sidransky, David ; Xing, Michael Mingzhao. / Uncommon mutation, but common amplifications, of the PIK3CA gene in thyroid tumors. In: Journal of Clinical Endocrinology and Metabolism. 2005 ; Vol. 90, No. 8. pp. 4688-4693.
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abstract = "Context: As in many other human cancers, overactivation of the phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway occurs frequently in thyroid cancer, but the mechanism is not completely clear. Objective: Because activating mutations and genomic amplification of the PIK3CA gene, which encodes the p110a catalytic subunit of PI3K, are common in many cancers, we sought to investigate this phenomenon in thyroid tumors. Design: To search for PIK3CA mutations, we isolated genomic DNA from primary thyroid tumors of various types and performed direct sequencing of the exons of PIK3CA gene that carry the most common mutations in other cancers. We used real-time quantitative PCR to investigate genomic amplification of the PIK3CA gene. Results: We found no PIK3CA gene mutations in 37 benign thyroid adenomas, 52 papillary thyroid cancers, 25 follicular thyroid cancers, 13 anaplastic thyroid cancers, 13 medullary thyroid cancers, and seven thyroid tumor cell lines. We found a C3075T single-nucleotide polymorphism in exon 20 of this gene in two cases. With a copy number of 4 or more defined as amplification, we found PIK3CA gene amplification in four of 34 (12{\%}) benign thyroid adenomas, three of 59 (5{\%}) papillary thyroid cancer, five of 21 (24{\%}) follicular thyroid cancer, none of 14 (0{\%}) medullary thyroid cancer, and five of seven (71{\%}) thyroid tumor cell lines. The PIK3CA gene amplification and consequent Akt activation were confirmed by fluorescence in situ hybridization and Western blotting studies using cell lines, respectively. Conclusion: These data suggest that mutation of the PIK3CA gene is not common, but its amplification is relatively common and may be a novel mechanism in activating the PI3K/Akt pathway in some thyroid tumors.",
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AU - Wu, Guojun

AU - Mambo, Elizabeth

AU - Guo, Zhongmin

AU - Hu, Shuiying

AU - Huang, Xin

AU - Gollin, Susanne M.

AU - Trink, Barry

AU - Ladenson, Paul W

AU - Sidransky, David

AU - Xing, Michael Mingzhao

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N2 - Context: As in many other human cancers, overactivation of the phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway occurs frequently in thyroid cancer, but the mechanism is not completely clear. Objective: Because activating mutations and genomic amplification of the PIK3CA gene, which encodes the p110a catalytic subunit of PI3K, are common in many cancers, we sought to investigate this phenomenon in thyroid tumors. Design: To search for PIK3CA mutations, we isolated genomic DNA from primary thyroid tumors of various types and performed direct sequencing of the exons of PIK3CA gene that carry the most common mutations in other cancers. We used real-time quantitative PCR to investigate genomic amplification of the PIK3CA gene. Results: We found no PIK3CA gene mutations in 37 benign thyroid adenomas, 52 papillary thyroid cancers, 25 follicular thyroid cancers, 13 anaplastic thyroid cancers, 13 medullary thyroid cancers, and seven thyroid tumor cell lines. We found a C3075T single-nucleotide polymorphism in exon 20 of this gene in two cases. With a copy number of 4 or more defined as amplification, we found PIK3CA gene amplification in four of 34 (12%) benign thyroid adenomas, three of 59 (5%) papillary thyroid cancer, five of 21 (24%) follicular thyroid cancer, none of 14 (0%) medullary thyroid cancer, and five of seven (71%) thyroid tumor cell lines. The PIK3CA gene amplification and consequent Akt activation were confirmed by fluorescence in situ hybridization and Western blotting studies using cell lines, respectively. Conclusion: These data suggest that mutation of the PIK3CA gene is not common, but its amplification is relatively common and may be a novel mechanism in activating the PI3K/Akt pathway in some thyroid tumors.

AB - Context: As in many other human cancers, overactivation of the phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway occurs frequently in thyroid cancer, but the mechanism is not completely clear. Objective: Because activating mutations and genomic amplification of the PIK3CA gene, which encodes the p110a catalytic subunit of PI3K, are common in many cancers, we sought to investigate this phenomenon in thyroid tumors. Design: To search for PIK3CA mutations, we isolated genomic DNA from primary thyroid tumors of various types and performed direct sequencing of the exons of PIK3CA gene that carry the most common mutations in other cancers. We used real-time quantitative PCR to investigate genomic amplification of the PIK3CA gene. Results: We found no PIK3CA gene mutations in 37 benign thyroid adenomas, 52 papillary thyroid cancers, 25 follicular thyroid cancers, 13 anaplastic thyroid cancers, 13 medullary thyroid cancers, and seven thyroid tumor cell lines. We found a C3075T single-nucleotide polymorphism in exon 20 of this gene in two cases. With a copy number of 4 or more defined as amplification, we found PIK3CA gene amplification in four of 34 (12%) benign thyroid adenomas, three of 59 (5%) papillary thyroid cancer, five of 21 (24%) follicular thyroid cancer, none of 14 (0%) medullary thyroid cancer, and five of seven (71%) thyroid tumor cell lines. The PIK3CA gene amplification and consequent Akt activation were confirmed by fluorescence in situ hybridization and Western blotting studies using cell lines, respectively. Conclusion: These data suggest that mutation of the PIK3CA gene is not common, but its amplification is relatively common and may be a novel mechanism in activating the PI3K/Akt pathway in some thyroid tumors.

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