Chromosomal rearrangements and copy number abnormalities of TP63 correlate with p63 protein expression in lung adenocarcinoma

Marie Christine Aubry, Anja Roden, Stephen J. Murphy, George Vasmatzis, Sarah H. Johnson, Faye R. Harris, Geoffrey Halling, Ryan A. Knudson, Rhett P. Ketterling, Andrew L Feldman

Research output: Contribution to journalArticle

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Abstract

The TP63 gene encodes a member of the p53 family of transcription factors. Although TP53 is a well-known tumor suppressor gene, the role of p63 in tumorigenesis is controversial. Our group recently identified novel chromosomal rearrangements involving TP63 in approximately 6% of peripheral T-cell lymphomas, which correlated with a p63+/p40- immunohistochemical profile. As a subset of lung adenocarcinomas are p63+/p40-, we undertook the current study to examine the presence of TP63 rearrangements and correlate with p63/p40 expression. Next-generation sequencing was used to identify genomic rearrangements of TP63 in 37 adenocarcinomas. Confirmatory fluorescence in-situ hybridization (FISH) using a break-apart probe to the TP63 gene region and immunohistochemistry for p63 and p40 were performed on adenocarcinomas with TP63 rearrangements identified by mate-pair sequencing. Immunohistochemistry for p63 and p40 was performed on 45 additional adenocarcinomas, and FISH was performed on all adenocarcinomas with p63 positivity. TP63 rearrangement was identified in two adenocarcinoma specimens from a single patient. The rearrangement resulted in a complex rearrangement of 3q that fused B3GALNT1 at the 3′ intron to TP63. FISH confirmed the rearrangement in both tumors. Immunohistochemistry staining for p63 was diffuse (>80% cells+) and p40 was negative. Of the 44 additional adenocarcinomas, 13 (30%) showed p63 expression; p40 was negative in all cases. No case showed rearrangement of TP63 by a break-apart FISH. However, extra copies of the intact TP63 locus were seen in the p63-positive areas of all 12 cases, with copy numbers ranging from three to seven. We have identified a novel chromosomal rearrangement involving TP63 in a p63+/p40- lung adenocarcinoma. Break-apart FISH testing can be used to diagnose this finding. Immunohistochemistry for p63 was not specific for this rearrangement, as nearly 33% of adenocarcinomas expressed p63. Additional copies of the intact TP63 locus were also a common finding and correlated with immunohistochemistry positivity for p63.

Original languageEnglish (US)
Pages (from-to)359-366
Number of pages8
JournalModern Pathology
Volume28
Issue number3
DOIs
StatePublished - Mar 1 2015

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Fluorescence In Situ Hybridization
Adenocarcinoma
Immunohistochemistry
Proteins
Peripheral T-Cell Lymphoma
adjuvant P40
Adenocarcinoma of lung
Tumor Suppressor Genes
Introns
Genes
Carcinogenesis
Transcription Factors
Staining and Labeling
Neoplasms

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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Chromosomal rearrangements and copy number abnormalities of TP63 correlate with p63 protein expression in lung adenocarcinoma. / Aubry, Marie Christine; Roden, Anja; Murphy, Stephen J.; Vasmatzis, George; Johnson, Sarah H.; Harris, Faye R.; Halling, Geoffrey; Knudson, Ryan A.; Ketterling, Rhett P.; Feldman, Andrew L.

In: Modern Pathology, Vol. 28, No. 3, 01.03.2015, p. 359-366.

Research output: Contribution to journalArticle

Aubry, Marie Christine ; Roden, Anja ; Murphy, Stephen J. ; Vasmatzis, George ; Johnson, Sarah H. ; Harris, Faye R. ; Halling, Geoffrey ; Knudson, Ryan A. ; Ketterling, Rhett P. ; Feldman, Andrew L. / Chromosomal rearrangements and copy number abnormalities of TP63 correlate with p63 protein expression in lung adenocarcinoma. In: Modern Pathology. 2015 ; Vol. 28, No. 3. pp. 359-366.
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abstract = "The TP63 gene encodes a member of the p53 family of transcription factors. Although TP53 is a well-known tumor suppressor gene, the role of p63 in tumorigenesis is controversial. Our group recently identified novel chromosomal rearrangements involving TP63 in approximately 6{\%} of peripheral T-cell lymphomas, which correlated with a p63+/p40- immunohistochemical profile. As a subset of lung adenocarcinomas are p63+/p40-, we undertook the current study to examine the presence of TP63 rearrangements and correlate with p63/p40 expression. Next-generation sequencing was used to identify genomic rearrangements of TP63 in 37 adenocarcinomas. Confirmatory fluorescence in-situ hybridization (FISH) using a break-apart probe to the TP63 gene region and immunohistochemistry for p63 and p40 were performed on adenocarcinomas with TP63 rearrangements identified by mate-pair sequencing. Immunohistochemistry for p63 and p40 was performed on 45 additional adenocarcinomas, and FISH was performed on all adenocarcinomas with p63 positivity. TP63 rearrangement was identified in two adenocarcinoma specimens from a single patient. The rearrangement resulted in a complex rearrangement of 3q that fused B3GALNT1 at the 3′ intron to TP63. FISH confirmed the rearrangement in both tumors. Immunohistochemistry staining for p63 was diffuse (>80{\%} cells+) and p40 was negative. Of the 44 additional adenocarcinomas, 13 (30{\%}) showed p63 expression; p40 was negative in all cases. No case showed rearrangement of TP63 by a break-apart FISH. However, extra copies of the intact TP63 locus were seen in the p63-positive areas of all 12 cases, with copy numbers ranging from three to seven. We have identified a novel chromosomal rearrangement involving TP63 in a p63+/p40- lung adenocarcinoma. Break-apart FISH testing can be used to diagnose this finding. Immunohistochemistry for p63 was not specific for this rearrangement, as nearly 33{\%} of adenocarcinomas expressed p63. Additional copies of the intact TP63 locus were also a common finding and correlated with immunohistochemistry positivity for p63.",
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AU - Aubry, Marie Christine

AU - Roden, Anja

AU - Murphy, Stephen J.

AU - Vasmatzis, George

AU - Johnson, Sarah H.

AU - Harris, Faye R.

AU - Halling, Geoffrey

AU - Knudson, Ryan A.

AU - Ketterling, Rhett P.

AU - Feldman, Andrew L

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