A high frequency of tumors with rearrangements of genes of the HMGI(Y) family in a series of 191 pulmonary chondroid hamartomas

Kazmierczak, Bernd; Meyer-Bolte, K.; Tran, Kim Hue; Wöckel, W; Breightman, Ilse; Rosigkeit, Jens; Bartnitzke, Sabine; Bullerdiek, Jörn

doi:10.1002/(sici)1098-2264(199910)26:2<125::aid-gcc4>3.0.co;2-a

Cited by 88 publications

(43 citation statements)

References 27 publications

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“…A similar phenomenon was also observed in pulmonary hamartomas of the lung, where hidden chromosomal inversions occurring together with simple translocations were also disclosed by FISH analysis. 33 CISH analysis on paraffin sections of this case revealed the same pattern, demonstrating that the in situ hybridization analysis is a powerful tool to assess PLAG1 rearrangements on paraffin-embedded archival tissues.…”

Section: Discussionsupporting

confidence: 60%

PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry

et al. 2005

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Pleomorphic adenoma is the most common benign tumor of the salivary glands. It has marked histological diversity with epithelial, myoepithelial and mesenchymal-type cells arranged in a variety of architectural and differentiation patterns. Pleomorphic adenoma gene 1 (PLAG1), shown to be consistently rearranged in pleomorphic adenomas, is activated by chromosomal translocations involving 8q12, the chromosome region that is most frequently affected in these tumors. In this study, we evaluated PLAG1 involvement in salivary gland tumorigenesis by determining the frequency of its alterations in a selected group of 20 salivary gland tumors: 16 pleomorphic adenomas and four carcinomas ex-pleomorphic adenoma, having in common the presence of karyotypic chromosome 8 deviations, either structural, with 8q12 rearrangements, or numerical, with gain of chromosome 8. PLAG1 status was analyzed using in situ hybridization techniques, on metaphase cells, by fluorescence detection and/or interphase cells in paraffin sections, by chromogenic detection. Except for one pleomorphic adenoma case (5%) that lacked PLAG1 involvement, 17 tumors (85%), (14 pleomorphic adenomas and three carcinomas ex-pleomorphic adenoma) showed intragenic rearrangements of PLAG1 and the remaining two cases (10%), (one pleomorphic adenoma and one carcinoma ex-pleomorphic adenoma), had chromosome trisomy 8 only. To further investigate the role of PLAG1 on pleomorphic adenomas tumorigenesis, as well as the putative morphogenesis mechanism, we attempted to identify the cell types (epithelial vs myoepithelial) carrying 8q12/PLAG1 abnormalities by a combined phenotypic/genotypic analysis in four cases (three pleomorphic adenoma and one carcinoma ex-pleomorphic adenoma) characterized by 8q12 translocations and PLAG1 rearrangement. In these cases, both cells populations carried PLAG1 rearrangements. This finding further supports the pluripotent single-cell theory, which postulates that the tumor-initiated, modified myoepithelial cell, evolves into the varied somatic cell phenotypes present in pleomorphic adenoma, and reinforces the role of PLAG1 on the tumorigenesis of benign and malignant pleomorphic adenoma.

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Section: Discussionsupporting

confidence: 60%

PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry

et al. 2005

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“…Rearrangements of 6p have been seen in several types of tumors of mesenchymal, epithelial, and hematopoietic origin among which are lipoma, uterine leiomyoma, hamartoma, pediatric renal epithelial neoplasm, ovarian carcinoma, and follicular lymphoma. [20][21][22][23][24][25][26][27][28][29][30][31][32] The putative oncogene, HMGIY (high mobility group protein isoforms I and Y), localized to 6p21 has been proposed to play a role in the development of a number of these neoplasms. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] An identical t(17;17)(q12;p13) was seen in two previous studies.…”

Section: Discussionmentioning

confidence: 99%

Cytogenetic and molecular cytogenetic findings in 43 aneurysmal bone cysts: aberrations of 17p mapped to 17p13.2 by fluorescence in situ hybridization

et al. 2004

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Aneurysmal bone cyst is a benign, cystic lesion of bone composed of blood-filled spaces separated by fibrous septa. Relatively few cases of aneurysmal bone cyst have been cytogenetically characterized, yet abnormalities of the short arm of chromosome 17 appear to be recurrent. In this study, conventional cytogenetic analysis of 43 aneurysmal bone cyst specimens from 38 patients over a 12-year period revealed clonal chromosomal abnormalities in 12 specimens. Karyotypic anomalies of 17p, including a complex translocation and inversion, were identified in eight of these 12 specimens. In an effort to further define the aberrant 17p breakpoint, fluorescence in situ hybridization (FISH) analyses were performed using a series of probe combinations spanning a 5.1 Mb region between the TP53 (17p13.1) and Miller-Dieker lissencephaly syndrome (17p13.3) gene loci. These studies revealed the critical breakpoint locus at 17p13.2, flanked proximally by an RP11-46I8, RP11-333E1, and RP11-457I18 bacterial artificial chromosome (BAC) probe cocktail and distally by an RP11-198F11 and RP11-115H24 BAC and RP5-1050D4 P1 artificial chromosome (PAC) probe cocktail. Overall, abnormalities of the 17p13.2 locus were identified by metaphase and/or interphase cell FISH analysis in 22 of 35 (63%) aneurysmal bone cyst specimens examined including 26 karyotypically normal specimens. These cytogenetic and molecular cytogenetic findings expand our knowledge of chromosomal alterations in aneurysmal bone cyst, further localize the critically involved 17p breakpoint, and provide an alternative approach (ie FISH) for detecting 17p abnormalities in nondividing cells of aneurysmal bone cysts. The latter could potentially be utilized as an adjunct in diagnostically challenging cases.

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“…It has therefore been suggested that the minimal requirement for tumorigenesis would be HMGI-C activation due to rearrangements, which leave intact at least exons 1-3 of the gene that code for the AT hook domains (Kazmierczak et al, 1996b;Rogalla et al, 1996). Breakpoints outside (usually upstream) of the coding region of HMGI-C have also been identified with chromosome aberrations mapped to the HMGI-C locus (Kazmierczak et al, 1999; Schoenberg Fejzo et a, Nuclear reactivity for HMGI-C in the neoplastic adipocytes of a lipoma (case 17L); t(2;12)(q35;q15) was identified in the tumor karyotype, FISH analysis was not performed. b, The corresponding immunohistochemical stain for HMGI(Y) is negative (case 17L).…”

Section: Discussionmentioning

confidence: 99%

HMGI-C and HMGI(Y) Immunoreactivity Correlates with Cytogenetic Abnormalities in Lipomas, Pulmonary Chondroid Hamartomas, Endometrial Polyps, and Uterine Leiomyomas and is Compatible with Rearrangement of the HMGI-C and HMGI(Y) Genes

Tallini

Vanni

Manfioletti

et al. 2000

Laboratory Investigation

134

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SUMMARY:High-mobility group (HMG) proteins are nonhistone nuclear proteins that play an important role in the regulation of chromatin structure and function. HMGI-C and HMGI(Y) are members of the HMGI family of HMG proteins, and their expression in adult tissues generally correlates with malignant tumor phenotypes. However, HMGI-C and HMGI(Y) dysregulation as a result of specific rearrangements involving 12q15 and 6p21, the respective chromosomal sites in which the HMGI-C and HMGI(Y) genes are located, is also identified in a variety of common benign mesenchymal tumors, such as lipomas and uterine leiomyomata. The general prevalence of HMGI-C and HMGI(Y) protein expression and its correlation with chromosomal alterations in these benign tumors are unknown. We analyzed 95 human tumors (20 lipomas, 21 pulmonary chondroid hamartomas, 26 uterine leiomyomata, and 28 endometrial polyps) representing a selection of the benign lesions in which karyotypic alterations involving the chromosomal regions 12q15 and 6p21 are frequently detected. All cases were successfully karyotyped and some of them analyzed by fluorescent in situ hybridization with probes spanning the HMGI-C and HMGI(Y) genes. The results of this study demonstrate that expression of HMGI-C or HMGI(Y) is a common occurrence in lipomas, pulmonary chondroid hamartomas, leiomyomata, and endometrial polyps; that it correlates with 12q15 and 6p21 chromosomal alterations (p Ͻ 0.001); and that it is compatible with rearrangement of the HMGI-C and HMGI(Y) genes. The expression pattern and cellular localization of the immunoreactivity support the view that in biphasic lesions composed of a mixture of both stromal and epithelial cells, such as pulmonary chondroid hamartoma and endometrial polyps, the mesenchymal component is the site of the HMGI genetic alterations. (Lab Invest 2000, 80:359-369).

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A high frequency of tumors with rearrangements of genes of the HMGI(Y) family in a series of 191 pulmonary chondroid hamartomas

Cited by 88 publications

References 27 publications

PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry

PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry

Cytogenetic and molecular cytogenetic findings in 43 aneurysmal bone cysts: aberrations of 17p mapped to 17p13.2 by fluorescence in situ hybridization

HMGI-C and HMGI(Y) Immunoreactivity Correlates with Cytogenetic Abnormalities in Lipomas, Pulmonary Chondroid Hamartomas, Endometrial Polyps, and Uterine Leiomyomas and is Compatible with Rearrangement of the HMGI-C and HMGI(Y) Genes

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