In silico analysis of ret variants in medullary thyroid cancer

From the computer to the bedside

Thomas E. Heineman, Rohan Joshi, Marc A. Cohen, William I. Kuhel, David I. Kutler

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective. The American Thyroid Association (ATA) medullary thyroid cancer (MTC) guidelines group RET variants, in the setting of familial medullary thyroid cancer and multiple endocrine neoplasia type 2, into 4 classes of severity based on epidemiological data. The aim of this study was to determine if genotype correlates with phenotype in RET missense mutations. Study Design. In silico mutational tolerance prediction. Setting. Academic research hospital. Subjects and Methods. We analyzed all RET variants currently listed in the ATA guidelines for the management of MTC using 2 computer-based (in silico) mutation tolerance prediction approaches: PolyPhen-2 HumVar and PolyPhen-2 HumDiv. Our analysis also included 27 different RET single-nucleotide polymorphisms resulting in missense variants. Results. There was a statistically significant difference in the overall HumDiv score between ATA groups A and B (P = .025) and a statistically significant different HumVar score between benign polymorphisms and ATA group A (P = .023). Overall, RET variants associated with a less aggressive clinical phenotype generally had a lower Hum Div/Var score. Conclusions. Polyphen-2 Hum Div/Var may provide additional clinical data to help distinguish benign from MEN2/familial medullary thyroid carcinoma-causing RET variants as well as less aggressive phenotypes (ATA A) from more aggressive ones (ATA B-C). In silico genetic analyses, with proper validation, may predict the phenotypic severity of RET variants, providing clinicians with a tool to aid clinical decision making in cases in which the RET variant is currently unknown or little epidemiological data are available

Original languageEnglish (US)
Pages (from-to)650-654
Number of pages5
JournalOtolaryngology - Head and Neck Surgery (United States)
Volume152
Issue number4
DOIs
StatePublished - Apr 7 2015
Externally publishedYes

Fingerprint

Computer Simulation
Thyroid Gland
Phenotype
Guidelines
Multiple Endocrine Neoplasia Type 2a
Missense Mutation
Single Nucleotide Polymorphism
Genotype
Medullary Thyroid cancer
Mutation
Research
Familial medullary thyroid carcinoma

Keywords

  • in silico analysis
  • medullary thyroid cancer
  • multiple endocrine neoplasia
  • RET gene
  • thyroidectomy

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

Cite this

In silico analysis of ret variants in medullary thyroid cancer : From the computer to the bedside. / Heineman, Thomas E.; Joshi, Rohan; Cohen, Marc A.; Kuhel, William I.; Kutler, David I.

In: Otolaryngology - Head and Neck Surgery (United States), Vol. 152, No. 4, 07.04.2015, p. 650-654.

Research output: Contribution to journalArticle

Heineman, Thomas E. ; Joshi, Rohan ; Cohen, Marc A. ; Kuhel, William I. ; Kutler, David I. / In silico analysis of ret variants in medullary thyroid cancer : From the computer to the bedside. In: Otolaryngology - Head and Neck Surgery (United States). 2015 ; Vol. 152, No. 4. pp. 650-654.
@article{21c795ee196e4fa486d97b67483f2683,
title = "In silico analysis of ret variants in medullary thyroid cancer: From the computer to the bedside",
abstract = "Objective. The American Thyroid Association (ATA) medullary thyroid cancer (MTC) guidelines group RET variants, in the setting of familial medullary thyroid cancer and multiple endocrine neoplasia type 2, into 4 classes of severity based on epidemiological data. The aim of this study was to determine if genotype correlates with phenotype in RET missense mutations. Study Design. In silico mutational tolerance prediction. Setting. Academic research hospital. Subjects and Methods. We analyzed all RET variants currently listed in the ATA guidelines for the management of MTC using 2 computer-based (in silico) mutation tolerance prediction approaches: PolyPhen-2 HumVar and PolyPhen-2 HumDiv. Our analysis also included 27 different RET single-nucleotide polymorphisms resulting in missense variants. Results. There was a statistically significant difference in the overall HumDiv score between ATA groups A and B (P = .025) and a statistically significant different HumVar score between benign polymorphisms and ATA group A (P = .023). Overall, RET variants associated with a less aggressive clinical phenotype generally had a lower Hum Div/Var score. Conclusions. Polyphen-2 Hum Div/Var may provide additional clinical data to help distinguish benign from MEN2/familial medullary thyroid carcinoma-causing RET variants as well as less aggressive phenotypes (ATA A) from more aggressive ones (ATA B-C). In silico genetic analyses, with proper validation, may predict the phenotypic severity of RET variants, providing clinicians with a tool to aid clinical decision making in cases in which the RET variant is currently unknown or little epidemiological data are available",
keywords = "in silico analysis, medullary thyroid cancer, multiple endocrine neoplasia, RET gene, thyroidectomy",
author = "Heineman, {Thomas E.} and Rohan Joshi and Cohen, {Marc A.} and Kuhel, {William I.} and Kutler, {David I.}",
year = "2015",
month = "4",
day = "7",
doi = "10.1177/0194599815569709",
language = "English (US)",
volume = "152",
pages = "650--654",
journal = "Otolaryngology - Head and Neck Surgery (United States)",
issn = "0194-5998",
publisher = "Mosby Inc.",
number = "4",

}

TY - JOUR

T1 - In silico analysis of ret variants in medullary thyroid cancer

T2 - From the computer to the bedside

AU - Heineman, Thomas E.

AU - Joshi, Rohan

AU - Cohen, Marc A.

AU - Kuhel, William I.

AU - Kutler, David I.

PY - 2015/4/7

Y1 - 2015/4/7

N2 - Objective. The American Thyroid Association (ATA) medullary thyroid cancer (MTC) guidelines group RET variants, in the setting of familial medullary thyroid cancer and multiple endocrine neoplasia type 2, into 4 classes of severity based on epidemiological data. The aim of this study was to determine if genotype correlates with phenotype in RET missense mutations. Study Design. In silico mutational tolerance prediction. Setting. Academic research hospital. Subjects and Methods. We analyzed all RET variants currently listed in the ATA guidelines for the management of MTC using 2 computer-based (in silico) mutation tolerance prediction approaches: PolyPhen-2 HumVar and PolyPhen-2 HumDiv. Our analysis also included 27 different RET single-nucleotide polymorphisms resulting in missense variants. Results. There was a statistically significant difference in the overall HumDiv score between ATA groups A and B (P = .025) and a statistically significant different HumVar score between benign polymorphisms and ATA group A (P = .023). Overall, RET variants associated with a less aggressive clinical phenotype generally had a lower Hum Div/Var score. Conclusions. Polyphen-2 Hum Div/Var may provide additional clinical data to help distinguish benign from MEN2/familial medullary thyroid carcinoma-causing RET variants as well as less aggressive phenotypes (ATA A) from more aggressive ones (ATA B-C). In silico genetic analyses, with proper validation, may predict the phenotypic severity of RET variants, providing clinicians with a tool to aid clinical decision making in cases in which the RET variant is currently unknown or little epidemiological data are available

AB - Objective. The American Thyroid Association (ATA) medullary thyroid cancer (MTC) guidelines group RET variants, in the setting of familial medullary thyroid cancer and multiple endocrine neoplasia type 2, into 4 classes of severity based on epidemiological data. The aim of this study was to determine if genotype correlates with phenotype in RET missense mutations. Study Design. In silico mutational tolerance prediction. Setting. Academic research hospital. Subjects and Methods. We analyzed all RET variants currently listed in the ATA guidelines for the management of MTC using 2 computer-based (in silico) mutation tolerance prediction approaches: PolyPhen-2 HumVar and PolyPhen-2 HumDiv. Our analysis also included 27 different RET single-nucleotide polymorphisms resulting in missense variants. Results. There was a statistically significant difference in the overall HumDiv score between ATA groups A and B (P = .025) and a statistically significant different HumVar score between benign polymorphisms and ATA group A (P = .023). Overall, RET variants associated with a less aggressive clinical phenotype generally had a lower Hum Div/Var score. Conclusions. Polyphen-2 Hum Div/Var may provide additional clinical data to help distinguish benign from MEN2/familial medullary thyroid carcinoma-causing RET variants as well as less aggressive phenotypes (ATA A) from more aggressive ones (ATA B-C). In silico genetic analyses, with proper validation, may predict the phenotypic severity of RET variants, providing clinicians with a tool to aid clinical decision making in cases in which the RET variant is currently unknown or little epidemiological data are available

KW - in silico analysis

KW - medullary thyroid cancer

KW - multiple endocrine neoplasia

KW - RET gene

KW - thyroidectomy

UR - http://www.scopus.com/inward/record.url?scp=84926314113&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84926314113&partnerID=8YFLogxK

U2 - 10.1177/0194599815569709

DO - 10.1177/0194599815569709

M3 - Article

VL - 152

SP - 650

EP - 654

JO - Otolaryngology - Head and Neck Surgery (United States)

JF - Otolaryngology - Head and Neck Surgery (United States)

SN - 0194-5998

IS - 4

ER -