Improved gene expression signature of testicular carcinoma in situ

TY - JOUR

T1 - Improved gene expression signature of testicular carcinoma in situ

AU - Almstrup, Kristian

AU - Leffers, Henrik

AU - Lothe, Ragnhild A

AU - Skakkebaek, Niels E

AU - Sonne, Si B

AU - Nielsen, John E

AU - Rajpert-De Meyts, Ewa

AU - Skotheim, Rolf I

N1 - Keywords: Base Sequence; Carcinoma in Situ; DNA Primers; Gene Expression Regulation, Neoplastic; Humans; Incidence; Male; Molecular Sequence Data; Neoplasms, Germ Cell and Embryonal; Oligonucleotide Array Sequence Analysis; Polyploidy; Reverse Transcriptase Polymerase Chain Reaction; Testicular Neoplasms

PY - 2007

Y1 - 2007

N2 - The carcinoma in situ (CIS) stage is the common precursor of testicular germ cell tumours (TGCTs) that arise in young adults. Within the past decade genome wide gene expression tools have been developed and have greatly advanced the insight into the biology of TGCTs. Two independent data sets on global gene expression in testicular CIS have been previously published. We have merged the two data sets on CIS samples (n = 6) and identified the shared gene expression signature in relation to expression in normal testis. Among the top-20 highest expressed genes, one-third was transcription factors and the list included some 'novel' CIS markers (i.e. DOCK11 and ANXA3). Genes related to biological terms 'nucleic acid binding' and 'translational activity' (e.g. transcription factors and ribosomal proteins, respectively) were consistently and significantly over-represented. Some of the significantly over-expressed genes in CIS cells were selected for validation by RT-PCR (IFI16, DOCK11, and ANXA3), immunohistochemistry (HLXB9), or in situ hybridization (IFI16). High-level analysis utilizing the Ingenuity pathway analysis tool indicated that networks relating to 'gene expression in cancer' and 'embryonic development' were significantly altered and could collectively affect cellular pathways like the WNT signalling cascade, which thus may be disrupted in testicular CIS. The merged CIS data from two different microarray platforms, to our knowledge, provide the most precise CIS gene expression signature to date.

AB - The carcinoma in situ (CIS) stage is the common precursor of testicular germ cell tumours (TGCTs) that arise in young adults. Within the past decade genome wide gene expression tools have been developed and have greatly advanced the insight into the biology of TGCTs. Two independent data sets on global gene expression in testicular CIS have been previously published. We have merged the two data sets on CIS samples (n = 6) and identified the shared gene expression signature in relation to expression in normal testis. Among the top-20 highest expressed genes, one-third was transcription factors and the list included some 'novel' CIS markers (i.e. DOCK11 and ANXA3). Genes related to biological terms 'nucleic acid binding' and 'translational activity' (e.g. transcription factors and ribosomal proteins, respectively) were consistently and significantly over-represented. Some of the significantly over-expressed genes in CIS cells were selected for validation by RT-PCR (IFI16, DOCK11, and ANXA3), immunohistochemistry (HLXB9), or in situ hybridization (IFI16). High-level analysis utilizing the Ingenuity pathway analysis tool indicated that networks relating to 'gene expression in cancer' and 'embryonic development' were significantly altered and could collectively affect cellular pathways like the WNT signalling cascade, which thus may be disrupted in testicular CIS. The merged CIS data from two different microarray platforms, to our knowledge, provide the most precise CIS gene expression signature to date.

U2 - 10.1111/j.1365-2605.2007.00758.x

DO - 10.1111/j.1365-2605.2007.00758.x

M3 - Journal article

C2 - 17488342

SN - 0105-6263

VL - 30

SP - 292

EP - 303

JO - International Journal of Andrology

JF - International Journal of Andrology

IS - 4

ER -