Sequence analysis of the PRKAR1A gene in sporadic somatotroph and other pituitary tumours

Gregory A. Kaltsas, Blerina Kola, Ninetta Borboli, Damian G. Morris, Maria Gueorguiev, Frankie M. Swords, S. Czirják, Lawrence S. Kirschner, Constantine A. Stratakis, Márta Korbonits, Ashley B. Grossman

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Abstract

OBJECTIVE: Carney complex (CNC) is an autosomal dominant multiple neoplasia syndrome featuring cardiac, endocrine, cutaneous and neural tumours, as well as a variety of pigmented lesions of the skin and mucosa. Pituitary GH-secreting tumours are found in approximately 10% of patients with CNC. One of the genes responsible for CNC, the PRKAR1A gene located on human chromosome 17q22-24, has recently been cloned. This represents a putative tumour suppressor gene, coding for the type 1α regulatory subunit of protein kinase A (PKA), which is found to be mutated in approximately half of the patients with CNC. However, it is currently unclear as to whether similar mutations occur in sporadic pituitary tumours. We have therefore investigated a series of GH-secreting and other pituitary tumours for sequence abnormalities in the PRKAR1A gene. The mRNA produced by the PRKAR1A undergoes decay if it codes for a truncated protein; we therefore also determined PRKAR1A mRNA levels in the tumours, and compared them with known mutant PRKAR1A-carrying lymphocyte samples. METHODS: We extracted RNA from a series of pituitary tumours, reverse transcribed it to cDNA, and directly sequenced the PRKAR1A coding sequence in 17 GH-secreting, three prolactin-secreting, three ACTH-secreting, one FSH-secreting and 10 nonfunctioning pituitary tumours. Lymphocyte and tumour tissue RNA from two patients with CNC was used as positive controls. Using duplex polymerase chain reaction (PCR) with the PRKAR1A and the 'housekeeping' gene GAPDH, we determined the relative expression of the PRKAR1A gene in the unknown as well as in the positive control samples. RESULTS AND CONCLUSION: No mutations were found in any of the exons sequenced. Relative mRNA expression was not decreased in any of the sporadic pituitary tumour samples. The present data thus do not suggest a major role for the PRKAR1A tumour suppressor gene in sporadic GH-secreting or other pituitary tumours.

Original languageEnglish
Pages (from-to)443-448
Number of pages6
JournalClinical Endocrinology
Volume57
Issue number4
DOIs
Publication statusPublished - 2002

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Somatotrophs
Carney Complex
Pituitary Neoplasms
Sequence Analysis
Genes
Neoplasms
Tumor Suppressor Genes
Messenger RNA
Lymphocytes
RNA
Skin
Mutation
Essential Genes
Human Chromosomes
Cyclic AMP-Dependent Protein Kinases
Prolactin
Adrenocorticotropic Hormone
Exons
Mucous Membrane
Complementary DNA

ASJC Scopus subject areas

  • Endocrinology

Cite this

Kaltsas, G. A., Kola, B., Borboli, N., Morris, D. G., Gueorguiev, M., Swords, F. M., ... Grossman, A. B. (2002). Sequence analysis of the PRKAR1A gene in sporadic somatotroph and other pituitary tumours. Clinical Endocrinology, 57(4), 443-448. https://doi.org/10.1046/j.1365-2265.2002.01643.x

Sequence analysis of the PRKAR1A gene in sporadic somatotroph and other pituitary tumours. / Kaltsas, Gregory A.; Kola, Blerina; Borboli, Ninetta; Morris, Damian G.; Gueorguiev, Maria; Swords, Frankie M.; Czirják, S.; Kirschner, Lawrence S.; Stratakis, Constantine A.; Korbonits, Márta; Grossman, Ashley B.

In: Clinical Endocrinology, Vol. 57, No. 4, 2002, p. 443-448.

Research output: Contribution to journalArticle

Kaltsas, GA, Kola, B, Borboli, N, Morris, DG, Gueorguiev, M, Swords, FM, Czirják, S, Kirschner, LS, Stratakis, CA, Korbonits, M & Grossman, AB 2002, 'Sequence analysis of the PRKAR1A gene in sporadic somatotroph and other pituitary tumours', Clinical Endocrinology, vol. 57, no. 4, pp. 443-448. https://doi.org/10.1046/j.1365-2265.2002.01643.x
Kaltsas, Gregory A. ; Kola, Blerina ; Borboli, Ninetta ; Morris, Damian G. ; Gueorguiev, Maria ; Swords, Frankie M. ; Czirják, S. ; Kirschner, Lawrence S. ; Stratakis, Constantine A. ; Korbonits, Márta ; Grossman, Ashley B. / Sequence analysis of the PRKAR1A gene in sporadic somatotroph and other pituitary tumours. In: Clinical Endocrinology. 2002 ; Vol. 57, No. 4. pp. 443-448.
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abstract = "OBJECTIVE: Carney complex (CNC) is an autosomal dominant multiple neoplasia syndrome featuring cardiac, endocrine, cutaneous and neural tumours, as well as a variety of pigmented lesions of the skin and mucosa. Pituitary GH-secreting tumours are found in approximately 10{\%} of patients with CNC. One of the genes responsible for CNC, the PRKAR1A gene located on human chromosome 17q22-24, has recently been cloned. This represents a putative tumour suppressor gene, coding for the type 1α regulatory subunit of protein kinase A (PKA), which is found to be mutated in approximately half of the patients with CNC. However, it is currently unclear as to whether similar mutations occur in sporadic pituitary tumours. We have therefore investigated a series of GH-secreting and other pituitary tumours for sequence abnormalities in the PRKAR1A gene. The mRNA produced by the PRKAR1A undergoes decay if it codes for a truncated protein; we therefore also determined PRKAR1A mRNA levels in the tumours, and compared them with known mutant PRKAR1A-carrying lymphocyte samples. METHODS: We extracted RNA from a series of pituitary tumours, reverse transcribed it to cDNA, and directly sequenced the PRKAR1A coding sequence in 17 GH-secreting, three prolactin-secreting, three ACTH-secreting, one FSH-secreting and 10 nonfunctioning pituitary tumours. Lymphocyte and tumour tissue RNA from two patients with CNC was used as positive controls. Using duplex polymerase chain reaction (PCR) with the PRKAR1A and the 'housekeeping' gene GAPDH, we determined the relative expression of the PRKAR1A gene in the unknown as well as in the positive control samples. RESULTS AND CONCLUSION: No mutations were found in any of the exons sequenced. Relative mRNA expression was not decreased in any of the sporadic pituitary tumour samples. The present data thus do not suggest a major role for the PRKAR1A tumour suppressor gene in sporadic GH-secreting or other pituitary tumours.",
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AU - Kaltsas, Gregory A.

AU - Kola, Blerina

AU - Borboli, Ninetta

AU - Morris, Damian G.

AU - Gueorguiev, Maria

AU - Swords, Frankie M.

AU - Czirják, S.

AU - Kirschner, Lawrence S.

AU - Stratakis, Constantine A.

AU - Korbonits, Márta

AU - Grossman, Ashley B.

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N2 - OBJECTIVE: Carney complex (CNC) is an autosomal dominant multiple neoplasia syndrome featuring cardiac, endocrine, cutaneous and neural tumours, as well as a variety of pigmented lesions of the skin and mucosa. Pituitary GH-secreting tumours are found in approximately 10% of patients with CNC. One of the genes responsible for CNC, the PRKAR1A gene located on human chromosome 17q22-24, has recently been cloned. This represents a putative tumour suppressor gene, coding for the type 1α regulatory subunit of protein kinase A (PKA), which is found to be mutated in approximately half of the patients with CNC. However, it is currently unclear as to whether similar mutations occur in sporadic pituitary tumours. We have therefore investigated a series of GH-secreting and other pituitary tumours for sequence abnormalities in the PRKAR1A gene. The mRNA produced by the PRKAR1A undergoes decay if it codes for a truncated protein; we therefore also determined PRKAR1A mRNA levels in the tumours, and compared them with known mutant PRKAR1A-carrying lymphocyte samples. METHODS: We extracted RNA from a series of pituitary tumours, reverse transcribed it to cDNA, and directly sequenced the PRKAR1A coding sequence in 17 GH-secreting, three prolactin-secreting, three ACTH-secreting, one FSH-secreting and 10 nonfunctioning pituitary tumours. Lymphocyte and tumour tissue RNA from two patients with CNC was used as positive controls. Using duplex polymerase chain reaction (PCR) with the PRKAR1A and the 'housekeeping' gene GAPDH, we determined the relative expression of the PRKAR1A gene in the unknown as well as in the positive control samples. RESULTS AND CONCLUSION: No mutations were found in any of the exons sequenced. Relative mRNA expression was not decreased in any of the sporadic pituitary tumour samples. The present data thus do not suggest a major role for the PRKAR1A tumour suppressor gene in sporadic GH-secreting or other pituitary tumours.

AB - OBJECTIVE: Carney complex (CNC) is an autosomal dominant multiple neoplasia syndrome featuring cardiac, endocrine, cutaneous and neural tumours, as well as a variety of pigmented lesions of the skin and mucosa. Pituitary GH-secreting tumours are found in approximately 10% of patients with CNC. One of the genes responsible for CNC, the PRKAR1A gene located on human chromosome 17q22-24, has recently been cloned. This represents a putative tumour suppressor gene, coding for the type 1α regulatory subunit of protein kinase A (PKA), which is found to be mutated in approximately half of the patients with CNC. However, it is currently unclear as to whether similar mutations occur in sporadic pituitary tumours. We have therefore investigated a series of GH-secreting and other pituitary tumours for sequence abnormalities in the PRKAR1A gene. The mRNA produced by the PRKAR1A undergoes decay if it codes for a truncated protein; we therefore also determined PRKAR1A mRNA levels in the tumours, and compared them with known mutant PRKAR1A-carrying lymphocyte samples. METHODS: We extracted RNA from a series of pituitary tumours, reverse transcribed it to cDNA, and directly sequenced the PRKAR1A coding sequence in 17 GH-secreting, three prolactin-secreting, three ACTH-secreting, one FSH-secreting and 10 nonfunctioning pituitary tumours. Lymphocyte and tumour tissue RNA from two patients with CNC was used as positive controls. Using duplex polymerase chain reaction (PCR) with the PRKAR1A and the 'housekeeping' gene GAPDH, we determined the relative expression of the PRKAR1A gene in the unknown as well as in the positive control samples. RESULTS AND CONCLUSION: No mutations were found in any of the exons sequenced. Relative mRNA expression was not decreased in any of the sporadic pituitary tumour samples. The present data thus do not suggest a major role for the PRKAR1A tumour suppressor gene in sporadic GH-secreting or other pituitary tumours.

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