BRAF mutations in an Italian cohort of thyroid cancers

Laura Fugazzola, Deborah Mannavola, Valentina Cirello, Guia Vannucchi, Marina Muzza, Leonardo Vicentini, Paolo Beck-Peccoz

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: Recently, a somatic point mutation of the BRAF gene (V599E) has been identified as the most common genetic event in papillary thyroid carcinoma (PTC) with a variable frequency (about 25-70%) in different series from USA, Japan, Portugal and Ukraine. DESIGN: In the present study, the genetic analysis of BRAF in an Italian cohort of 65 thyroid tumours with corresponding normal tissues and 21 thyroid benign disorders is reported. METHODS: For BRAF analysis, the somatic DNA was PCR amplified by means of specific intronic primers and PCR products were directly sequenced. Statistical analyses were obtained by means of Fisher's exact test. RESULTS: All mutations detected involved a T > A transversion at 1796 (V599E) and were heterozygous. Overall, BRAF V599E mutation was found in 18/58 (32.1%) PTCs. According to the histological type of the tumour, the mutation was present in 38.3% of cases of conventional PTC (18/47), in 0/6 follicular variant of PTC, in 0/ 3 oncocytic variant of PTC. No BRAF mutations were detected either in five follicular carcinomas, or in four poorly differentiated or undifferentiated cancers or in benign thyroid disorders. No statistically significant correlation of BRAF mutation with patient age and gender, with multicentricity of the tumour, with the lymphocytic infiltration of the tissue, with the stage and with the recurrence rate, was found. BRAFV599E tended to be associated, although not significantly, with a greater volume and extension of the tumour and with lymph-nodal metastases at surgery. CONCLUSIONS: In conclusion, the present study on the first Italian series of thyroid cancers shows a frequency of 38.3% of BRAFV599E in the classical variant of PTC, confirming the key role of this mutation in promoting tumourigenesis.

Original languageEnglish
Pages (from-to)239-243
Number of pages5
JournalClinical Endocrinology
Volume61
Issue number2
DOIs
Publication statusPublished - Aug 2004

Fingerprint

Thyroid Neoplasms
Mutation
Thyroid Gland
Neoplasms
Ukraine
Polymerase Chain Reaction
Factor IX
Portugal
Lymph
Tumor Burden
Point Mutation
Japan
Papillary Thyroid cancer
Neoplasm Metastasis
Carcinoma
Recurrence
DNA
Genes

ASJC Scopus subject areas

  • Endocrinology

Cite this

Fugazzola, L., Mannavola, D., Cirello, V., Vannucchi, G., Muzza, M., Vicentini, L., & Beck-Peccoz, P. (2004). BRAF mutations in an Italian cohort of thyroid cancers. Clinical Endocrinology, 61(2), 239-243. https://doi.org/10.1111/j.1365-2265.2004.02089.x

BRAF mutations in an Italian cohort of thyroid cancers. / Fugazzola, Laura; Mannavola, Deborah; Cirello, Valentina; Vannucchi, Guia; Muzza, Marina; Vicentini, Leonardo; Beck-Peccoz, Paolo.

In: Clinical Endocrinology, Vol. 61, No. 2, 08.2004, p. 239-243.

Research output: Contribution to journalArticle

Fugazzola, L, Mannavola, D, Cirello, V, Vannucchi, G, Muzza, M, Vicentini, L & Beck-Peccoz, P 2004, 'BRAF mutations in an Italian cohort of thyroid cancers', Clinical Endocrinology, vol. 61, no. 2, pp. 239-243. https://doi.org/10.1111/j.1365-2265.2004.02089.x
Fugazzola L, Mannavola D, Cirello V, Vannucchi G, Muzza M, Vicentini L et al. BRAF mutations in an Italian cohort of thyroid cancers. Clinical Endocrinology. 2004 Aug;61(2):239-243. https://doi.org/10.1111/j.1365-2265.2004.02089.x
Fugazzola, Laura ; Mannavola, Deborah ; Cirello, Valentina ; Vannucchi, Guia ; Muzza, Marina ; Vicentini, Leonardo ; Beck-Peccoz, Paolo. / BRAF mutations in an Italian cohort of thyroid cancers. In: Clinical Endocrinology. 2004 ; Vol. 61, No. 2. pp. 239-243.
@article{12da2c19e28b4eebab3f8e7dabce800a,
title = "BRAF mutations in an Italian cohort of thyroid cancers",
abstract = "OBJECTIVE: Recently, a somatic point mutation of the BRAF gene (V599E) has been identified as the most common genetic event in papillary thyroid carcinoma (PTC) with a variable frequency (about 25-70{\%}) in different series from USA, Japan, Portugal and Ukraine. DESIGN: In the present study, the genetic analysis of BRAF in an Italian cohort of 65 thyroid tumours with corresponding normal tissues and 21 thyroid benign disorders is reported. METHODS: For BRAF analysis, the somatic DNA was PCR amplified by means of specific intronic primers and PCR products were directly sequenced. Statistical analyses were obtained by means of Fisher's exact test. RESULTS: All mutations detected involved a T > A transversion at 1796 (V599E) and were heterozygous. Overall, BRAF V599E mutation was found in 18/58 (32.1{\%}) PTCs. According to the histological type of the tumour, the mutation was present in 38.3{\%} of cases of conventional PTC (18/47), in 0/6 follicular variant of PTC, in 0/ 3 oncocytic variant of PTC. No BRAF mutations were detected either in five follicular carcinomas, or in four poorly differentiated or undifferentiated cancers or in benign thyroid disorders. No statistically significant correlation of BRAF mutation with patient age and gender, with multicentricity of the tumour, with the lymphocytic infiltration of the tissue, with the stage and with the recurrence rate, was found. BRAFV599E tended to be associated, although not significantly, with a greater volume and extension of the tumour and with lymph-nodal metastases at surgery. CONCLUSIONS: In conclusion, the present study on the first Italian series of thyroid cancers shows a frequency of 38.3{\%} of BRAFV599E in the classical variant of PTC, confirming the key role of this mutation in promoting tumourigenesis.",
author = "Laura Fugazzola and Deborah Mannavola and Valentina Cirello and Guia Vannucchi and Marina Muzza and Leonardo Vicentini and Paolo Beck-Peccoz",
year = "2004",
month = "8",
doi = "10.1111/j.1365-2265.2004.02089.x",
language = "English",
volume = "61",
pages = "239--243",
journal = "Clinical Endocrinology",
issn = "0300-0664",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - BRAF mutations in an Italian cohort of thyroid cancers

AU - Fugazzola, Laura

AU - Mannavola, Deborah

AU - Cirello, Valentina

AU - Vannucchi, Guia

AU - Muzza, Marina

AU - Vicentini, Leonardo

AU - Beck-Peccoz, Paolo

PY - 2004/8

Y1 - 2004/8

N2 - OBJECTIVE: Recently, a somatic point mutation of the BRAF gene (V599E) has been identified as the most common genetic event in papillary thyroid carcinoma (PTC) with a variable frequency (about 25-70%) in different series from USA, Japan, Portugal and Ukraine. DESIGN: In the present study, the genetic analysis of BRAF in an Italian cohort of 65 thyroid tumours with corresponding normal tissues and 21 thyroid benign disorders is reported. METHODS: For BRAF analysis, the somatic DNA was PCR amplified by means of specific intronic primers and PCR products were directly sequenced. Statistical analyses were obtained by means of Fisher's exact test. RESULTS: All mutations detected involved a T > A transversion at 1796 (V599E) and were heterozygous. Overall, BRAF V599E mutation was found in 18/58 (32.1%) PTCs. According to the histological type of the tumour, the mutation was present in 38.3% of cases of conventional PTC (18/47), in 0/6 follicular variant of PTC, in 0/ 3 oncocytic variant of PTC. No BRAF mutations were detected either in five follicular carcinomas, or in four poorly differentiated or undifferentiated cancers or in benign thyroid disorders. No statistically significant correlation of BRAF mutation with patient age and gender, with multicentricity of the tumour, with the lymphocytic infiltration of the tissue, with the stage and with the recurrence rate, was found. BRAFV599E tended to be associated, although not significantly, with a greater volume and extension of the tumour and with lymph-nodal metastases at surgery. CONCLUSIONS: In conclusion, the present study on the first Italian series of thyroid cancers shows a frequency of 38.3% of BRAFV599E in the classical variant of PTC, confirming the key role of this mutation in promoting tumourigenesis.

AB - OBJECTIVE: Recently, a somatic point mutation of the BRAF gene (V599E) has been identified as the most common genetic event in papillary thyroid carcinoma (PTC) with a variable frequency (about 25-70%) in different series from USA, Japan, Portugal and Ukraine. DESIGN: In the present study, the genetic analysis of BRAF in an Italian cohort of 65 thyroid tumours with corresponding normal tissues and 21 thyroid benign disorders is reported. METHODS: For BRAF analysis, the somatic DNA was PCR amplified by means of specific intronic primers and PCR products were directly sequenced. Statistical analyses were obtained by means of Fisher's exact test. RESULTS: All mutations detected involved a T > A transversion at 1796 (V599E) and were heterozygous. Overall, BRAF V599E mutation was found in 18/58 (32.1%) PTCs. According to the histological type of the tumour, the mutation was present in 38.3% of cases of conventional PTC (18/47), in 0/6 follicular variant of PTC, in 0/ 3 oncocytic variant of PTC. No BRAF mutations were detected either in five follicular carcinomas, or in four poorly differentiated or undifferentiated cancers or in benign thyroid disorders. No statistically significant correlation of BRAF mutation with patient age and gender, with multicentricity of the tumour, with the lymphocytic infiltration of the tissue, with the stage and with the recurrence rate, was found. BRAFV599E tended to be associated, although not significantly, with a greater volume and extension of the tumour and with lymph-nodal metastases at surgery. CONCLUSIONS: In conclusion, the present study on the first Italian series of thyroid cancers shows a frequency of 38.3% of BRAFV599E in the classical variant of PTC, confirming the key role of this mutation in promoting tumourigenesis.

UR - http://www.scopus.com/inward/record.url?scp=4143051232&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4143051232&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2265.2004.02089.x

DO - 10.1111/j.1365-2265.2004.02089.x

M3 - Article

C2 - 15272920

AN - SCOPUS:4143051232

VL - 61

SP - 239

EP - 243

JO - Clinical Endocrinology

JF - Clinical Endocrinology

SN - 0300-0664

IS - 2

ER -