Testicular germ cell tumours of adolescents and adults
Section: Section of Molecular Carcinogenesis
Testicular germ cell tumours of adolescents and adults (TGCTs) are the most common tumour in young men and with an increasing incidence reported. The prognosis for TGCT is good although 20-30% of patients presenting with metastatic disease will die of the malignancy. TGCT can be classified into the two main histological categories of seminoma and nonseminoma. Seminoma resemble primordial germ cells and nonseminoma are composed of neoplastic tissues exhibiting somatic, embryonal or extraembryonal tissues. Primordial germ cells are generally considered to be the cells of origin of TGCT and are believed to give rise to Intratubular Germ Cell Neoplasia Undifferentiated (IGCNU), the precursor lesion of both seminoma and nonseminoma.
Identifying genes involved in the development of testicular germ cell tumours
Our analyses are consistent with gain of 12p material being critical in the development of invasive testicular germ cell tumours of adults and adolescents from IGCNU. Analysis of invasive cases with gain of the entire short arm of 12p and cases with amplification 12p11.2-12.1 has identified a minimum overlapping region of gain and a number of overexpressed genes that might be involved in tumour progression, including KRAS2. Other frequent minimum regions of genetic imbalance have been identified throughout the rest of the genome. These regions include 4q12 which we have shown in some cases involves gain of only the KIT gene and not immediately flanking genes. The selective involvement of KIT in the progression of at least some seminomas is indicated. Through analysis of a large number of samples we have also identified relationships between activating mutations, copy number and expression levels of genes indicative of aberrant MAP kinase signalling in TGCTs. Further analyses of candidate genes and pathways indicated and the effects of interfering with these are ongoing.
Enlarge image: Definition of 4q12 amplification in a testicular germ cell tumour 35KB
In the Section of Molecular Carcinogenesis
