Whole exome sequencing and single nucleotide polymorphism array analyses to identify germline alterations in genes associated with testosterone metabolism in a patient with androgen insensitivity syndrome and early-onset colorectal cancer

Vittoria Disciglio, Andrea Devecchi, Orazio Palumbo, Massimo Carella, Donata Penso, Massimo Milione, Giorgio Valle, Marco Alessandro Pierotti, Marco Vitellaro, Lucio Bertario, Silvana Canevari, Stefano Signoroni, Loris De Cecco

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Androgen insensitivity syndrome (AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor (AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer (CRC) have been described.

CASE PRESENTATION: Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a microRNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human cancers.

CONCLUSIONS: By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis.

Original languageEnglish
Pages (from-to)51
JournalChinese Journal of Cancer
Volume35
Issue number1
DOIs
Publication statusPublished - Jun 7 2016

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Androgen-Insensitivity Syndrome
Exome
Single Nucleotide Polymorphism
Testosterone
Colorectal Neoplasms
Genes
Neoplasm Genes
Androgen Receptors
Disorders of Sex Development
Mutation
Germ-Line Mutation
Pedigree
MicroRNAs
Oncogenes
Neoplasms
Chromosomes

Keywords

  • Journal Article

Cite this

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title = "Whole exome sequencing and single nucleotide polymorphism array analyses to identify germline alterations in genes associated with testosterone metabolism in a patient with androgen insensitivity syndrome and early-onset colorectal cancer",
abstract = "BACKGROUND: Androgen insensitivity syndrome (AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor (AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer (CRC) have been described.CASE PRESENTATION: Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a microRNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human cancers.CONCLUSIONS: By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis.",
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author = "Vittoria Disciglio and Andrea Devecchi and Orazio Palumbo and Massimo Carella and Donata Penso and Massimo Milione and Giorgio Valle and Pierotti, {Marco Alessandro} and Marco Vitellaro and Lucio Bertario and Silvana Canevari and Stefano Signoroni and {De Cecco}, Loris",
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T1 - Whole exome sequencing and single nucleotide polymorphism array analyses to identify germline alterations in genes associated with testosterone metabolism in a patient with androgen insensitivity syndrome and early-onset colorectal cancer

AU - Disciglio, Vittoria

AU - Devecchi, Andrea

AU - Palumbo, Orazio

AU - Carella, Massimo

AU - Penso, Donata

AU - Milione, Massimo

AU - Valle, Giorgio

AU - Pierotti, Marco Alessandro

AU - Vitellaro, Marco

AU - Bertario, Lucio

AU - Canevari, Silvana

AU - Signoroni, Stefano

AU - De Cecco, Loris

PY - 2016/6/7

Y1 - 2016/6/7

N2 - BACKGROUND: Androgen insensitivity syndrome (AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor (AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer (CRC) have been described.CASE PRESENTATION: Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a microRNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human cancers.CONCLUSIONS: By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis.

AB - BACKGROUND: Androgen insensitivity syndrome (AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor (AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer (CRC) have been described.CASE PRESENTATION: Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a microRNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human cancers.CONCLUSIONS: By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis.

KW - Journal Article

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DO - 10.1186/s40880-016-0115-1

M3 - Article

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SN - 1000-467X

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