Loss of heterozygosity analysis identifies genetic abnormalities in mycosis fungoides and specific loci associated with disease progression

Terrence M. Katona, Dennis P. O'Malley, Liang Cheng, Kim M. Hiatt, Mingsheng Wang, John J. Anagnostou, Steven D. Billings, Bruce R. Smoller

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Mycosis fungoides (MF) exhibits a variety of underlying molecular defects. Loss of heterozygosity (LOH) is a technique used to detect chromosomal imbalances in neoplastic disorders using archival tissue. We analyzed skin biopsies of MF in different stages for the presence of LOH at specific loci to evaluate underlying genetic aberrations involved in MF and its progression. Twenty-five skin biopsies (15 plaque stage and 10 tumor stage) from 19 patients were evaluated. LOH was examined at 1p22 (D1S2766), 9p21 [IFNA, p15 (D9S1748), p16 (D9S171)], 10q23 [PTEN (D10S185, D10S541, D10S2491)], and 17p13 [p53 (TP53)]. Abnormal lymphocytes were microdissected from formalin-fixed, paraffin-embedded tissue sections. Sixteen of the 25 (64%) specimens evaluated had at least one abnormal LOH locus and LOH was identified in 7 of 15 (47%) plaque and in 9 of 10 (90%) tumor stage lesions, respectively. All 3 patients with sequential biopsies (plaque followed by tumor lesions) had additional LOH abnormalities in tumor specimens compared with plaque stage lesions. LOH most frequently involved chromosome 10, including 7 of 10 (70%) tumor stage lesions. Loss of multiple alleles was only identified in tumor stage cases, with 3 tumors undergoing allelic losses at 3 separate loci. Our results suggest that LOH studies are a robust method for evaluating genetic abnormalities in MF. Tumor stage lesions manifest increasing allelic losses compared with plaque stage. Further, in this series, several loci associated with the tumor suppressor gene PTEN on chromosome 10 appear to be associated with progression from plaque to tumor stage.

Original languageEnglish
Pages (from-to)1552-1556
Number of pages5
JournalAmerican Journal of Surgical Pathology
Volume31
Issue number10
DOIs
StatePublished - Oct 2007

Fingerprint

Mycosis Fungoides
Loss of Heterozygosity
Disease Progression
Neoplasms
Chromosomes, Human, Pair 10
Biopsy
Skin
Tumor Suppressor Genes
Paraffin
Formaldehyde
Alleles
Lymphocytes

Keywords

  • Cutaneous lymphoma
  • Genetics
  • Loss of heterozygosity
  • Molecular
  • Mycosis fungoides
  • Plaque
  • Progression
  • Tumor
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine

Cite this

Loss of heterozygosity analysis identifies genetic abnormalities in mycosis fungoides and specific loci associated with disease progression. / Katona, Terrence M.; O'Malley, Dennis P.; Cheng, Liang; Hiatt, Kim M.; Wang, Mingsheng; Anagnostou, John J.; Billings, Steven D.; Smoller, Bruce R.

In: American Journal of Surgical Pathology, Vol. 31, No. 10, 10.2007, p. 1552-1556.

Research output: Contribution to journalArticle

Katona, Terrence M. ; O'Malley, Dennis P. ; Cheng, Liang ; Hiatt, Kim M. ; Wang, Mingsheng ; Anagnostou, John J. ; Billings, Steven D. ; Smoller, Bruce R. / Loss of heterozygosity analysis identifies genetic abnormalities in mycosis fungoides and specific loci associated with disease progression. In: American Journal of Surgical Pathology. 2007 ; Vol. 31, No. 10. pp. 1552-1556.
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abstract = "Mycosis fungoides (MF) exhibits a variety of underlying molecular defects. Loss of heterozygosity (LOH) is a technique used to detect chromosomal imbalances in neoplastic disorders using archival tissue. We analyzed skin biopsies of MF in different stages for the presence of LOH at specific loci to evaluate underlying genetic aberrations involved in MF and its progression. Twenty-five skin biopsies (15 plaque stage and 10 tumor stage) from 19 patients were evaluated. LOH was examined at 1p22 (D1S2766), 9p21 [IFNA, p15 (D9S1748), p16 (D9S171)], 10q23 [PTEN (D10S185, D10S541, D10S2491)], and 17p13 [p53 (TP53)]. Abnormal lymphocytes were microdissected from formalin-fixed, paraffin-embedded tissue sections. Sixteen of the 25 (64{\%}) specimens evaluated had at least one abnormal LOH locus and LOH was identified in 7 of 15 (47{\%}) plaque and in 9 of 10 (90{\%}) tumor stage lesions, respectively. All 3 patients with sequential biopsies (plaque followed by tumor lesions) had additional LOH abnormalities in tumor specimens compared with plaque stage lesions. LOH most frequently involved chromosome 10, including 7 of 10 (70{\%}) tumor stage lesions. Loss of multiple alleles was only identified in tumor stage cases, with 3 tumors undergoing allelic losses at 3 separate loci. Our results suggest that LOH studies are a robust method for evaluating genetic abnormalities in MF. Tumor stage lesions manifest increasing allelic losses compared with plaque stage. Further, in this series, several loci associated with the tumor suppressor gene PTEN on chromosome 10 appear to be associated with progression from plaque to tumor stage.",
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AU - Katona, Terrence M.

AU - O'Malley, Dennis P.

AU - Cheng, Liang

AU - Hiatt, Kim M.

AU - Wang, Mingsheng

AU - Anagnostou, John J.

AU - Billings, Steven D.

AU - Smoller, Bruce R.

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AB - Mycosis fungoides (MF) exhibits a variety of underlying molecular defects. Loss of heterozygosity (LOH) is a technique used to detect chromosomal imbalances in neoplastic disorders using archival tissue. We analyzed skin biopsies of MF in different stages for the presence of LOH at specific loci to evaluate underlying genetic aberrations involved in MF and its progression. Twenty-five skin biopsies (15 plaque stage and 10 tumor stage) from 19 patients were evaluated. LOH was examined at 1p22 (D1S2766), 9p21 [IFNA, p15 (D9S1748), p16 (D9S171)], 10q23 [PTEN (D10S185, D10S541, D10S2491)], and 17p13 [p53 (TP53)]. Abnormal lymphocytes were microdissected from formalin-fixed, paraffin-embedded tissue sections. Sixteen of the 25 (64%) specimens evaluated had at least one abnormal LOH locus and LOH was identified in 7 of 15 (47%) plaque and in 9 of 10 (90%) tumor stage lesions, respectively. All 3 patients with sequential biopsies (plaque followed by tumor lesions) had additional LOH abnormalities in tumor specimens compared with plaque stage lesions. LOH most frequently involved chromosome 10, including 7 of 10 (70%) tumor stage lesions. Loss of multiple alleles was only identified in tumor stage cases, with 3 tumors undergoing allelic losses at 3 separate loci. Our results suggest that LOH studies are a robust method for evaluating genetic abnormalities in MF. Tumor stage lesions manifest increasing allelic losses compared with plaque stage. Further, in this series, several loci associated with the tumor suppressor gene PTEN on chromosome 10 appear to be associated with progression from plaque to tumor stage.

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