Molecular genetic evidence supporting the origin of somatic-type malignancy and teratoma from the same progenitor cell

Jennifer B. Kum, Thomas Ulbright, Sean R. Williamson, Mingsheng Wang, Shaobo Zhang, Richard Foster, David Grignon, John Eble, Stephen D W Beck, Liang Cheng

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Abstract

Occasionally, testicular teratomas have been observed to occur in association with somatic-type malignancies. The latter may be seen in the primary germ cell tumor or, more commonly, in metastases after chemotherapy. The molecular-genetic relationship between the teratoma and the somatic-type malignancy is uncertain. We examined 27 pairs of teratoma and somatic-type malignancies in metastatic lesions. Interphase fluorescence in situ hybridization (FISH) analysis for 12p overexpression and i(12p) was performed on formalin-fixed, paraffin-embedded specimens. In addition, we compared the pattern of allelic loss between the teratoma and the somatic-type malignancy using 4 microsatellite DNA markers (D1S508, interferon-α, D13S317, and D18S543). A laser capture microdissection technique was used to procure separate tumor components. The somatic-type malignancies included adenocarcinoma (13), primitive neuroectodermal tumor (5), sarcoma not otherwise specified (5), squamous cell carcinoma (1), chondrosarcoma (1), and rhabdomyosarcoma (2). Twenty-one of 27 tumor pairs (78%) showed a similar pattern of overexpression of 12p and/or i(12p) in both components. Two of the 27 (7%) tumor pairs showed i(12p) only in the teratomatous component, and 4 of the 27 (15%) tumor pairs showed no abnormalities of chromosome 12p by interphase FISH. Eight of the 12 (67%) tumor pairs analyzed had identical patterns of loss of heterozygosity in both the teratoma and the somatic-type malignancy. Four of the 12 (33%) paired cases showed additional allelic loss at the interferon-α locus in the somatic-type malignant component only. Our data show that the somatic-type malignancies that develop in germ cell tumors have the same genetic alterations, detectable by FISH and loss of heterozygosity studies, as in the corresponding teratoma. These findings support that the somatic-type malignancies within metastases and the teratomas are clonally related and likely derived from a common progenitor cell. Interphase FISH can be performed on formalin-fixed, paraffin-embedded tissue and is a sensitive method for detecting 12p overexpression and i(12p), thus aiding in establishing the germ cell origin of somatic-type malignancies in this context.

Original languageEnglish
Pages (from-to)1849-1856
Number of pages8
JournalAmerican Journal of Surgical Pathology
Volume36
Issue number12
DOIs
StatePublished - Dec 2012

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Teratoma
Molecular Biology
Stem Cells
Neoplasms
Loss of Heterozygosity
Fluorescence In Situ Hybridization
Interphase
Germ Cell and Embryonal Neoplasms
Paraffin
Interferons
Formaldehyde
Neoplasm Metastasis
Laser Capture Microdissection
Primitive Neuroectodermal Tumors
Chondrosarcoma
Genetic Markers
Germ Cells
Chromosome Aberrations
Sarcoma
Microsatellite Repeats

Keywords

  • clonal origin
  • isochromosome 12p
  • laser capture microdissection
  • loss of heterozygosity
  • mixed germ cell tumor
  • molecular genetics
  • somatic malignancy/secondary malignant component
  • teratoma
  • testis

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery

Cite this

@article{034f264e076f4d0495c60c0e22ce0bff,
title = "Molecular genetic evidence supporting the origin of somatic-type malignancy and teratoma from the same progenitor cell",
abstract = "Occasionally, testicular teratomas have been observed to occur in association with somatic-type malignancies. The latter may be seen in the primary germ cell tumor or, more commonly, in metastases after chemotherapy. The molecular-genetic relationship between the teratoma and the somatic-type malignancy is uncertain. We examined 27 pairs of teratoma and somatic-type malignancies in metastatic lesions. Interphase fluorescence in situ hybridization (FISH) analysis for 12p overexpression and i(12p) was performed on formalin-fixed, paraffin-embedded specimens. In addition, we compared the pattern of allelic loss between the teratoma and the somatic-type malignancy using 4 microsatellite DNA markers (D1S508, interferon-α, D13S317, and D18S543). A laser capture microdissection technique was used to procure separate tumor components. The somatic-type malignancies included adenocarcinoma (13), primitive neuroectodermal tumor (5), sarcoma not otherwise specified (5), squamous cell carcinoma (1), chondrosarcoma (1), and rhabdomyosarcoma (2). Twenty-one of 27 tumor pairs (78{\%}) showed a similar pattern of overexpression of 12p and/or i(12p) in both components. Two of the 27 (7{\%}) tumor pairs showed i(12p) only in the teratomatous component, and 4 of the 27 (15{\%}) tumor pairs showed no abnormalities of chromosome 12p by interphase FISH. Eight of the 12 (67{\%}) tumor pairs analyzed had identical patterns of loss of heterozygosity in both the teratoma and the somatic-type malignancy. Four of the 12 (33{\%}) paired cases showed additional allelic loss at the interferon-α locus in the somatic-type malignant component only. Our data show that the somatic-type malignancies that develop in germ cell tumors have the same genetic alterations, detectable by FISH and loss of heterozygosity studies, as in the corresponding teratoma. These findings support that the somatic-type malignancies within metastases and the teratomas are clonally related and likely derived from a common progenitor cell. Interphase FISH can be performed on formalin-fixed, paraffin-embedded tissue and is a sensitive method for detecting 12p overexpression and i(12p), thus aiding in establishing the germ cell origin of somatic-type malignancies in this context.",
keywords = "clonal origin, isochromosome 12p, laser capture microdissection, loss of heterozygosity, mixed germ cell tumor, molecular genetics, somatic malignancy/secondary malignant component, teratoma, testis",
author = "Kum, {Jennifer B.} and Thomas Ulbright and Williamson, {Sean R.} and Mingsheng Wang and Shaobo Zhang and Richard Foster and David Grignon and John Eble and Beck, {Stephen D W} and Liang Cheng",
year = "2012",
month = "12",
doi = "10.1097/PAS.0b013e31826df1ab",
language = "English",
volume = "36",
pages = "1849--1856",
journal = "American Journal of Surgical Pathology",
issn = "0147-5185",
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TY - JOUR

T1 - Molecular genetic evidence supporting the origin of somatic-type malignancy and teratoma from the same progenitor cell

AU - Kum, Jennifer B.

AU - Ulbright, Thomas

AU - Williamson, Sean R.

AU - Wang, Mingsheng

AU - Zhang, Shaobo

AU - Foster, Richard

AU - Grignon, David

AU - Eble, John

AU - Beck, Stephen D W

AU - Cheng, Liang

PY - 2012/12

Y1 - 2012/12

N2 - Occasionally, testicular teratomas have been observed to occur in association with somatic-type malignancies. The latter may be seen in the primary germ cell tumor or, more commonly, in metastases after chemotherapy. The molecular-genetic relationship between the teratoma and the somatic-type malignancy is uncertain. We examined 27 pairs of teratoma and somatic-type malignancies in metastatic lesions. Interphase fluorescence in situ hybridization (FISH) analysis for 12p overexpression and i(12p) was performed on formalin-fixed, paraffin-embedded specimens. In addition, we compared the pattern of allelic loss between the teratoma and the somatic-type malignancy using 4 microsatellite DNA markers (D1S508, interferon-α, D13S317, and D18S543). A laser capture microdissection technique was used to procure separate tumor components. The somatic-type malignancies included adenocarcinoma (13), primitive neuroectodermal tumor (5), sarcoma not otherwise specified (5), squamous cell carcinoma (1), chondrosarcoma (1), and rhabdomyosarcoma (2). Twenty-one of 27 tumor pairs (78%) showed a similar pattern of overexpression of 12p and/or i(12p) in both components. Two of the 27 (7%) tumor pairs showed i(12p) only in the teratomatous component, and 4 of the 27 (15%) tumor pairs showed no abnormalities of chromosome 12p by interphase FISH. Eight of the 12 (67%) tumor pairs analyzed had identical patterns of loss of heterozygosity in both the teratoma and the somatic-type malignancy. Four of the 12 (33%) paired cases showed additional allelic loss at the interferon-α locus in the somatic-type malignant component only. Our data show that the somatic-type malignancies that develop in germ cell tumors have the same genetic alterations, detectable by FISH and loss of heterozygosity studies, as in the corresponding teratoma. These findings support that the somatic-type malignancies within metastases and the teratomas are clonally related and likely derived from a common progenitor cell. Interphase FISH can be performed on formalin-fixed, paraffin-embedded tissue and is a sensitive method for detecting 12p overexpression and i(12p), thus aiding in establishing the germ cell origin of somatic-type malignancies in this context.

AB - Occasionally, testicular teratomas have been observed to occur in association with somatic-type malignancies. The latter may be seen in the primary germ cell tumor or, more commonly, in metastases after chemotherapy. The molecular-genetic relationship between the teratoma and the somatic-type malignancy is uncertain. We examined 27 pairs of teratoma and somatic-type malignancies in metastatic lesions. Interphase fluorescence in situ hybridization (FISH) analysis for 12p overexpression and i(12p) was performed on formalin-fixed, paraffin-embedded specimens. In addition, we compared the pattern of allelic loss between the teratoma and the somatic-type malignancy using 4 microsatellite DNA markers (D1S508, interferon-α, D13S317, and D18S543). A laser capture microdissection technique was used to procure separate tumor components. The somatic-type malignancies included adenocarcinoma (13), primitive neuroectodermal tumor (5), sarcoma not otherwise specified (5), squamous cell carcinoma (1), chondrosarcoma (1), and rhabdomyosarcoma (2). Twenty-one of 27 tumor pairs (78%) showed a similar pattern of overexpression of 12p and/or i(12p) in both components. Two of the 27 (7%) tumor pairs showed i(12p) only in the teratomatous component, and 4 of the 27 (15%) tumor pairs showed no abnormalities of chromosome 12p by interphase FISH. Eight of the 12 (67%) tumor pairs analyzed had identical patterns of loss of heterozygosity in both the teratoma and the somatic-type malignancy. Four of the 12 (33%) paired cases showed additional allelic loss at the interferon-α locus in the somatic-type malignant component only. Our data show that the somatic-type malignancies that develop in germ cell tumors have the same genetic alterations, detectable by FISH and loss of heterozygosity studies, as in the corresponding teratoma. These findings support that the somatic-type malignancies within metastases and the teratomas are clonally related and likely derived from a common progenitor cell. Interphase FISH can be performed on formalin-fixed, paraffin-embedded tissue and is a sensitive method for detecting 12p overexpression and i(12p), thus aiding in establishing the germ cell origin of somatic-type malignancies in this context.

KW - clonal origin

KW - isochromosome 12p

KW - laser capture microdissection

KW - loss of heterozygosity

KW - mixed germ cell tumor

KW - molecular genetics

KW - somatic malignancy/secondary malignant component

KW - teratoma

KW - testis

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U2 - 10.1097/PAS.0b013e31826df1ab

DO - 10.1097/PAS.0b013e31826df1ab

M3 - Article

VL - 36

SP - 1849

EP - 1856

JO - American Journal of Surgical Pathology

JF - American Journal of Surgical Pathology

SN - 0147-5185

IS - 12

ER -