Whole exome sequencing andsingle nucleotide polymorphism array analyses toidentify germline alterations ingenes associated withtestosterone metabolism ina patient withandrogen insensitivity syndrome andearly-onset colorectal cancer
10.1186/s40880-016-0115-1
- Author:
Disciglio VITTORIA
1
;
Devecchi ANDREA
;
Palumbo ORAZIO
;
Carella MASSIMO
;
DonataPenso
;
MassimoMilione
;
GiorgioValle
;
MarcoAlessandroPierotti
;
MarcoVitellaro
;
Bertario LUCIO
;
Canevari SILVANA
;
Signoroni STEFANO
;
LorisDeCecco
Author Information
1. Department of Experimental Oncology and Molecular Medicine
- Keywords:
Androgen insensitivity syndrome;
Androgen receptor;
Colorectal cancer;
Single nucleotide polymorphism array;
Testosterone;
Whole exome sequencing
- From:Chinese Journal of Cancer
2016;35(10):546-559
- CountryChina
- Language:Chinese
-
Abstract:
Background:Androgen insensitivity syndrome (AIS), a disorder of sexual development in 46, XYindividuals, 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 ifrst cousin was diagnosed with AIS and harbored the sameAR 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 identiifed. 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 identiifed 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.
