TY - JOUR

T1 - Epigenetic features of testicular germ cell tumours in relation to epigenetic characteristics of foetal germ cells

AU - Kristensen, Dina G.

AU - Skakkebæk, Niels E.

AU - Rajpert-De Meyts, Ewa

AU - Almstrup, Kristian

PY - 2013

Y1 - 2013

N2 - Foetal development of germ cells is a unique biological process orchestrated by cel-lular specification, migration and niche development in concert with extensive epigenetic and transcriptional programs. Many of these processes take place early in foetal life and are hence very difficult to study in humans. However, the common precursor of testicular cancers-the carcinoma in situ (CIS) cell-is thought to be an arrested foetal germ cell. Therefore studies of CIS cells may leverage information on human foetal germ cell development and, in particular, when neoplastic transformation is initiated. In this review, we will focus on current knowledge of the epigenetics of CIS cells and relate it to the epigenetic changes occurring in early developing germ cells of mice during specification, migration and colonization. We will focus on DNA methylation and some of the best studied histone modifications like H3K9me2, H3K27me3 and H3K9ac. We also show that CIS cells contain high levels of H3K27ac, which is known to mark active enhancers. Proper epigen-etic reprogramming seems to be a pre-requisite of normal foetal germ cell development and we propose that alterations in these programs may be a pathogenic event in the initiation of testicular germ cell cancer. Even though only sparse information is available on epigenetic cues in human foetal germ cells, these indicate that the developmental patterns differ from the findings in mice and emphasize the need for further studies of foetal germ cell development in humans.

AB - Foetal development of germ cells is a unique biological process orchestrated by cel-lular specification, migration and niche development in concert with extensive epigenetic and transcriptional programs. Many of these processes take place early in foetal life and are hence very difficult to study in humans. However, the common precursor of testicular cancers-the carcinoma in situ (CIS) cell-is thought to be an arrested foetal germ cell. Therefore studies of CIS cells may leverage information on human foetal germ cell development and, in particular, when neoplastic transformation is initiated. In this review, we will focus on current knowledge of the epigenetics of CIS cells and relate it to the epigenetic changes occurring in early developing germ cells of mice during specification, migration and colonization. We will focus on DNA methylation and some of the best studied histone modifications like H3K9me2, H3K27me3 and H3K9ac. We also show that CIS cells contain high levels of H3K27ac, which is known to mark active enhancers. Proper epigen-etic reprogramming seems to be a pre-requisite of normal foetal germ cell development and we propose that alterations in these programs may be a pathogenic event in the initiation of testicular germ cell cancer. Even though only sparse information is available on epigenetic cues in human foetal germ cells, these indicate that the developmental patterns differ from the findings in mice and emphasize the need for further studies of foetal germ cell development in humans.

KW - Carcinoma in situ testis

KW - Epigenetics

KW - Gonocyte

KW - Primordial germ cell

U2 - 10.1387/ijdb.130142ka

DO - 10.1387/ijdb.130142ka

M3 - Journal article

C2 - 23784842

AN - SCOPUS:84880060821

VL - 57

SP - 309

EP - 317

JO - International Journal of Developmental Biology

JF - International Journal of Developmental Biology

SN - 0214-6282

IS - 2-4

ER -