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

Cancer Communications

Lucio Bertario¹  Giorgio Valle²  Stefano Signoroni³  Vittoria Disciglio³  Donata Penso³  Andrea Devecchi³  Massimo Milione⁴  Marco Alessandro Pierotti⁵  Loris De Cecco⁶  Marco Vitellaro⁶  Silvana Canevari⁶  Orazio Palumbo⁷  Massimo Carella⁷ 

[1] Colorectal Surgery Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;Department of Biology, University of Padova, Padua, Italy;Department of Experimental Oncology and Molecular Medicine, Functional Genomics and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;Hereditary Digestive Tract Tumors Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo FG, Italy

关键词: Androgen insensitivity syndrome;    Androgen receptor;    Colorectal cancer;    Single nucleotide polymorphism array;    Testosterone;    Whole exome sequencing;   

DOI  :  10.1186/s40880-016-0115-1

学科分类：肿瘤学

来源: Springer

【 摘 要 】

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. 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. 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.

【 授权许可】

CC BY