Analysis of gene expression profiles of microdissected cell populations indicates that testicular carcinoma in situ is an arrested gonocyte

Si Brask Sonne; Kristian Almstrup; Marlene Dalgaard; Agnieszka Sierakowska Juncker; Daniel Edsgard; Ludmila Ruban; Neil J Harrison; Christian Schwager; Amir Abdollahi; Peter E Huber; Søren Brunak; Lise Mette Gjerdrum; Harry D Moore; Peter W Andrews; Niels E Skakkebaek; Ewa Rajpert-De Meyts; Henrik Leffers; Si Brask Sonne; Kristian Almstrup; Marlene Dalgaard; Agnieszka Sierakowska Juncker; Daniel Edsgard; Ludmila Ruban; Neil J Harrison; Christian Schwager; Amir Abdollahi; Peter E Huber; Søren Brunak; Lise Mette Gjerdrum; Harry D Moore; Peter W Andrews; Niels E Skakkebaek; Ewa Rajpert-De Meyts; Henrik Leffers

doi:10.1158/0008-5472.CAN-08-4554

Analysis of gene expression profiles of microdissected cell populations indicates that testicular carcinoma in situ is an arrested gonocyte

Si Brask Sonne, Kristian Almstrup, Marlene Dalgaard, Agnieszka Sierakowska Juncker, Daniel Edsgard, Ludmila Ruban, Neil J Harrison, Christian Schwager, Amir Abdollahi, Peter E Huber, Søren Brunak, Lise Mette Gjerdrum, Harry D Moore, Peter W Andrews, Niels E Skakkebaek, Ewa Rajpert-De Meyts, Henrik Leffers, Si Brask Sonne, Kristian Almstrup, Marlene DalgaardAgnieszka Sierakowska Juncker, Daniel Edsgard, Ludmila Ruban, Neil J Harrison, Christian Schwager, Amir Abdollahi, Peter E Huber, Søren Brunak, Lise Mette Gjerdrum, Harry D Moore, Peter W Andrews, Niels E Skakkebaek, Ewa Rajpert-De Meyts, Henrik Leffers

136 Citations (Scopus)

Abstract

Testicular germ cell cancers in young adult men derive from a precursor lesion called carcinoma in situ (CIS) of the testis. CIS cells were suggested to arise from primordial germ cells or gonocytes. However, direct studies on purified samples of CIS cells are lacking. To overcome this problem, we performed laser microdissection of CIS cells. Highly enriched cell populations were obtained and subjected to gene expression analysis. The expression profile of CIS cells was compared with microdissected gonocytes, oogonia, and cultured embryonic stem cells with and without genomic aberrations. Three samples of each tissue type were used for the analyses. Unique expression patterns for these developmentally very related cell types revealed that CIS cells were very similar to gonocytes because only five genes distinguished these two cell types. We did not find indications that CIS was derived from a meiotic cell, and the similarity to embryonic stem cells was modest compared with gonocytes. Thus, we provide new evidence that the molecular phenotype of CIS cells is similar to that of gonocytes. Our data are in line with the idea that CIS cells may be gonocytes that survived in the postnatal testis. We speculate that disturbed development of somatic cells in the fetal testis may play a role in allowing undifferentiated cells to survive in the postnatal testes. The further development of CIS into invasive germ cell tumors may depend on signals from their postpubertal niche of somatic cells, including hormones and growth factors from Leydig and Sertoli cells.

Original language	English
Book series	Current Cancer Research
Volume	69
Issue number	12
Pages (from-to)	5241-50
Number of pages	10
ISSN	0940-0745
DOIs	https://doi.org/10.1158/0008-5472.CAN-08-4554 https://doi.org/10.1158/0008-5472.CAN-08-4554
Publication status	Published - 15 Jun 2009

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Sonne, S. B., Almstrup, K., Dalgaard, M., Juncker, A. S., Edsgard, D., Ruban, L., Harrison, N. J., Schwager, C., Abdollahi, A., Huber, P. E., Brunak, S., Gjerdrum, L. M., Moore, H. D., Andrews, P. W., Skakkebaek, N. E., Rajpert-De Meyts, E., Leffers, H., Sonne, S. B., Almstrup, K., ... Leffers, H. (2009). Analysis of gene expression profiles of microdissected cell populations indicates that testicular carcinoma in situ is an arrested gonocyte. Current Cancer Research, 69(12), 5241-50. https://doi.org/10.1158/0008-5472.CAN-08-4554, https://doi.org/10.1158/0008-5472.CAN-08-4554

Sonne, SB, Almstrup, K, Dalgaard, M, Juncker, AS, Edsgard, D, Ruban, L, Harrison, NJ, Schwager, C, Abdollahi, A, Huber, PE, Brunak, S, Gjerdrum, LM, Moore, HD, Andrews, PW, Skakkebaek, NE, Rajpert-De Meyts, E, Leffers, H, Sonne, SB, Almstrup, K, Dalgaard, M, Juncker, AS, Edsgard, D, Ruban, L, Harrison, NJ, Schwager, C, Abdollahi, A, Huber, PE, Brunak, S, Gjerdrum, LM, Moore, HD, Andrews, PW, Skakkebaek, NE, Rajpert-De Meyts, E & Leffers, H 2009, 'Analysis of gene expression profiles of microdissected cell populations indicates that testicular carcinoma in situ is an arrested gonocyte', Current Cancer Research, vol. 69, no. 12, pp. 5241-50. https://doi.org/10.1158/0008-5472.CAN-08-4554, https://doi.org/10.1158/0008-5472.CAN-08-4554

@article{fa6613001f8111df8ed1000ea68e967b,

title = "Analysis of gene expression profiles of microdissected cell populations indicates that testicular carcinoma in situ is an arrested gonocyte",

abstract = "Testicular germ cell cancers in young adult men derive from a precursor lesion called carcinoma in situ (CIS) of the testis. CIS cells were suggested to arise from primordial germ cells or gonocytes. However, direct studies on purified samples of CIS cells are lacking. To overcome this problem, we performed laser microdissection of CIS cells. Highly enriched cell populations were obtained and subjected to gene expression analysis. The expression profile of CIS cells was compared with microdissected gonocytes, oogonia, and cultured embryonic stem cells with and without genomic aberrations. Three samples of each tissue type were used for the analyses. Unique expression patterns for these developmentally very related cell types revealed that CIS cells were very similar to gonocytes because only five genes distinguished these two cell types. We did not find indications that CIS was derived from a meiotic cell, and the similarity to embryonic stem cells was modest compared with gonocytes. Thus, we provide new evidence that the molecular phenotype of CIS cells is similar to that of gonocytes. Our data are in line with the idea that CIS cells may be gonocytes that survived in the postnatal testis. We speculate that disturbed development of somatic cells in the fetal testis may play a role in allowing undifferentiated cells to survive in the postnatal testes. The further development of CIS into invasive germ cell tumors may depend on signals from their postpubertal niche of somatic cells, including hormones and growth factors from Leydig and Sertoli cells.",

author = "Sonne, {Si Brask} and Kristian Almstrup and Marlene Dalgaard and Juncker, {Agnieszka Sierakowska} and Daniel Edsgard and Ludmila Ruban and Harrison, {Neil J} and Christian Schwager and Amir Abdollahi and Huber, {Peter E} and S{\o}ren Brunak and Gjerdrum, {Lise Mette} and Moore, {Harry D} and Andrews, {Peter W} and Skakkebaek, {Niels E} and {Rajpert-De Meyts}, Ewa and Henrik Leffers and Sonne, {Si Brask} and Kristian Almstrup and Marlene Dalgaard and Juncker, {Agnieszka Sierakowska} and Daniel Edsgard and Ludmila Ruban and Harrison, {Neil J} and Christian Schwager and Amir Abdollahi and Huber, {Peter E} and S{\o}ren Brunak and Gjerdrum, {Lise Mette} and Moore, {Harry D} and Andrews, {Peter W} and Skakkebaek, {Niels E} and {Rajpert-De Meyts}, Ewa and Henrik Leffers",

note = "Keywords: Base Sequence; DNA Primers; Gene Expression Profiling; Humans; Immunochemistry; In Situ Hybridization; Male; Reverse Transcriptase Polymerase Chain Reaction; Testicular Neoplasms",

year = "2009",

month = jun,

day = "15",

doi = "10.1158/0008-5472.CAN-08-4554",

language = "English",

volume = "69",

pages = "5241--50",

journal = "Current Cancer Research",

issn = "0940-0745",

publisher = "Springer Publishing Company",

number = "12",

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TY - JOUR

T1 - Analysis of gene expression profiles of microdissected cell populations indicates that testicular carcinoma in situ is an arrested gonocyte

AU - Sonne, Si Brask

AU - Almstrup, Kristian

AU - Dalgaard, Marlene

AU - Juncker, Agnieszka Sierakowska

AU - Edsgard, Daniel

AU - Ruban, Ludmila

AU - Harrison, Neil J

AU - Schwager, Christian

AU - Abdollahi, Amir

AU - Huber, Peter E

AU - Brunak, Søren

AU - Gjerdrum, Lise Mette

AU - Moore, Harry D

AU - Andrews, Peter W

AU - Skakkebaek, Niels E

AU - Rajpert-De Meyts, Ewa

AU - Leffers, Henrik

AU - Sonne, Si Brask

AU - Almstrup, Kristian

AU - Dalgaard, Marlene

AU - Juncker, Agnieszka Sierakowska

AU - Edsgard, Daniel

AU - Ruban, Ludmila

AU - Harrison, Neil J

AU - Schwager, Christian

AU - Abdollahi, Amir

AU - Huber, Peter E

AU - Brunak, Søren

AU - Gjerdrum, Lise Mette

AU - Moore, Harry D

AU - Andrews, Peter W

AU - Skakkebaek, Niels E

AU - Rajpert-De Meyts, Ewa

AU - Leffers, Henrik

N1 - Keywords: Base Sequence; DNA Primers; Gene Expression Profiling; Humans; Immunochemistry; In Situ Hybridization; Male; Reverse Transcriptase Polymerase Chain Reaction; Testicular Neoplasms

PY - 2009/6/15

Y1 - 2009/6/15

N2 - Testicular germ cell cancers in young adult men derive from a precursor lesion called carcinoma in situ (CIS) of the testis. CIS cells were suggested to arise from primordial germ cells or gonocytes. However, direct studies on purified samples of CIS cells are lacking. To overcome this problem, we performed laser microdissection of CIS cells. Highly enriched cell populations were obtained and subjected to gene expression analysis. The expression profile of CIS cells was compared with microdissected gonocytes, oogonia, and cultured embryonic stem cells with and without genomic aberrations. Three samples of each tissue type were used for the analyses. Unique expression patterns for these developmentally very related cell types revealed that CIS cells were very similar to gonocytes because only five genes distinguished these two cell types. We did not find indications that CIS was derived from a meiotic cell, and the similarity to embryonic stem cells was modest compared with gonocytes. Thus, we provide new evidence that the molecular phenotype of CIS cells is similar to that of gonocytes. Our data are in line with the idea that CIS cells may be gonocytes that survived in the postnatal testis. We speculate that disturbed development of somatic cells in the fetal testis may play a role in allowing undifferentiated cells to survive in the postnatal testes. The further development of CIS into invasive germ cell tumors may depend on signals from their postpubertal niche of somatic cells, including hormones and growth factors from Leydig and Sertoli cells.

AB - Testicular germ cell cancers in young adult men derive from a precursor lesion called carcinoma in situ (CIS) of the testis. CIS cells were suggested to arise from primordial germ cells or gonocytes. However, direct studies on purified samples of CIS cells are lacking. To overcome this problem, we performed laser microdissection of CIS cells. Highly enriched cell populations were obtained and subjected to gene expression analysis. The expression profile of CIS cells was compared with microdissected gonocytes, oogonia, and cultured embryonic stem cells with and without genomic aberrations. Three samples of each tissue type were used for the analyses. Unique expression patterns for these developmentally very related cell types revealed that CIS cells were very similar to gonocytes because only five genes distinguished these two cell types. We did not find indications that CIS was derived from a meiotic cell, and the similarity to embryonic stem cells was modest compared with gonocytes. Thus, we provide new evidence that the molecular phenotype of CIS cells is similar to that of gonocytes. Our data are in line with the idea that CIS cells may be gonocytes that survived in the postnatal testis. We speculate that disturbed development of somatic cells in the fetal testis may play a role in allowing undifferentiated cells to survive in the postnatal testes. The further development of CIS into invasive germ cell tumors may depend on signals from their postpubertal niche of somatic cells, including hormones and growth factors from Leydig and Sertoli cells.

U2 - 10.1158/0008-5472.CAN-08-4554

DO - 10.1158/0008-5472.CAN-08-4554

M3 - Journal article

C2 - 19491264

SN - 0940-0745

VL - 69

SP - 5241

EP - 5250

JO - Current Cancer Research

JF - Current Cancer Research

IS - 12

ER -

Analysis of gene expression profiles of microdissected cell populations indicates that testicular carcinoma in situ is an arrested gonocyte

Abstract

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