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) hav...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2016-06-01
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| Series: | Chinese Journal of Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40880-016-0115-1 |
| _version_ | 1818910917098733568 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Vittoria Disciglio |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T22:50:25Z |
| format | Article |
| id | doaj.art-86481dddaf534cb89770ecf1441a2485 |
| institution | Directory Open Access Journal |
| issn | 1944-446X |
| language | English |
| last_indexed | 2024-12-19T22:50:25Z |
| publishDate | 2016-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Journal of Cancer |
| spelling | doaj.art-86481dddaf534cb89770ecf1441a24852022-12-21T20:02:50ZengBMCChinese Journal of Cancer1944-446X2016-06-0135111410.1186/s40880-016-0115-1Whole 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 cancerVittoria Disciglio0Andrea Devecchi1Orazio Palumbo2Massimo Carella3Donata Penso4Massimo Milione5Giorgio Valle6Marco Alessandro Pierotti7Marco Vitellaro8Lucio Bertario9Silvana Canevari10Stefano Signoroni11Loris De Cecco12Department of Experimental Oncology and Molecular Medicine, Functional Genomics and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei TumoriDepartment of Experimental Oncology and Molecular Medicine, Functional Genomics and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei TumoriMedical Genetics Unit, IRCCS Casa Sollievo della SofferenzaMedical Genetics Unit, IRCCS Casa Sollievo della SofferenzaDepartment of Experimental Oncology and Molecular Medicine, Functional Genomics and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei TumoriDepartment of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale TumoriDepartment of Biology, University of PadovaFondazione IRCCS Istituto Nazionale dei TumoriHereditary Digestive Tract Tumors Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei TumoriHereditary Digestive Tract Tumors Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei TumoriDepartment of Experimental Oncology and Molecular Medicine, Functional Genomics and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei TumoriHereditary Digestive Tract Tumors Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei TumoriDepartment of Experimental Oncology and Molecular Medicine, Functional Genomics and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei TumoriAbstract 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.http://link.springer.com/article/10.1186/s40880-016-0115-1Androgen insensitivity syndromeAndrogen receptorColorectal cancerSingle nucleotide polymorphism arrayTestosteroneWhole exome sequencing |
| spellingShingle | 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 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 Chinese Journal of Cancer Androgen insensitivity syndrome Androgen receptor Colorectal cancer Single nucleotide polymorphism array Testosterone Whole exome sequencing |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Androgen insensitivity syndrome Androgen receptor Colorectal cancer Single nucleotide polymorphism array Testosterone Whole exome sequencing |
| url | http://link.springer.com/article/10.1186/s40880-016-0115-1 |
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