Loss of expression of the SWI/SNF chromatin remodeling subunit BRG1/SMARCA4 is frequently observed in intraductal papillary mucinous neoplasms of the pancreas

Marco Dal Molin, Seung Mo Hong, Sachidanand Hebbar, Rajni Sharma, Francesca Scrimieri, Roeland F. De Wilde, Skye Mayo, Michael Goggins, Christopher L. Wolfgang, Richard D. Schulick, Ming Tseh Lin, James R. Eshleman, Ralph H. Hruban, Anirban Maitra, Hanno Matthaei

Research output: Contribution to journalArticle

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Abstract

A better molecular characterization of intraductal papillary mucinous neoplasm (IPMN), the most frequent cystic precursor lesion of pancreatic adenocarcinoma, may have a pivotal role in its early detection and in the development of effective therapeutic strategies. BRG1, a central component of the chromatin remodeling complex SWI/SNF regulating transcription, is inactive in several malignancies. In this study, we evaluate the Brg1 expression in intraductal papillary mucinous neoplasm to better understand its role in the pancreatic carcinogenesis. Tissue microarrays of 66 surgically resected IPMNs were immunolabeled for the Brg1 protein. Expression patterns were then correlated with clinicopathologic parameters. Normal pancreatic epithelium strongly immunolabeled for Brg1. Reduced Brg1 expression was observed in 32 (53.3%) of the 60 evaluable IPMN lesions and occurred more frequently in high-grade IPMNs (13 of 17 showed loss; 76%) compared to intermediate-grade (15 of 29 showed loss; 52%) and low-grade IPMNs (4 of 14 showed loss; 28%) (P =.03). A complete loss of Brg1 expression was observed in 5 (8.3%) of the 60 lesions. Finally, a decrease in Brg1 protein expression was furthermore found in a low-passage noninvasive IPMN cell line by Western blot analysis. We did not observe correlation between Brg1 expression and IPMN subtype or with location of the cyst. We provide first evidence that Brg1 expression is lost in noninvasive cystic precursor lesions of pancreatic adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)585-591
Number of pages7
JournalHuman Pathology
Volume43
Issue number4
DOIs
StatePublished - Apr 2012
Externally publishedYes

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Chromatin Assembly and Disassembly
Pancreatic Neoplasms
Neoplasms
Adenocarcinoma
Cysts
Carcinogenesis
Proteins
Epithelium
Western Blotting
Cell Line

Keywords

  • BRG1
  • IPMN
  • Pancreatic cancer

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Loss of expression of the SWI/SNF chromatin remodeling subunit BRG1/SMARCA4 is frequently observed in intraductal papillary mucinous neoplasms of the pancreas. / Dal Molin, Marco; Hong, Seung Mo; Hebbar, Sachidanand; Sharma, Rajni; Scrimieri, Francesca; De Wilde, Roeland F.; Mayo, Skye; Goggins, Michael; Wolfgang, Christopher L.; Schulick, Richard D.; Lin, Ming Tseh; Eshleman, James R.; Hruban, Ralph H.; Maitra, Anirban; Matthaei, Hanno.

In: Human Pathology, Vol. 43, No. 4, 04.2012, p. 585-591.

Research output: Contribution to journalArticle

Dal Molin, M, Hong, SM, Hebbar, S, Sharma, R, Scrimieri, F, De Wilde, RF, Mayo, S, Goggins, M, Wolfgang, CL, Schulick, RD, Lin, MT, Eshleman, JR, Hruban, RH, Maitra, A & Matthaei, H 2012, 'Loss of expression of the SWI/SNF chromatin remodeling subunit BRG1/SMARCA4 is frequently observed in intraductal papillary mucinous neoplasms of the pancreas', Human Pathology, vol. 43, no. 4, pp. 585-591. https://doi.org/10.1016/j.humpath.2011.06.009
Dal Molin, Marco ; Hong, Seung Mo ; Hebbar, Sachidanand ; Sharma, Rajni ; Scrimieri, Francesca ; De Wilde, Roeland F. ; Mayo, Skye ; Goggins, Michael ; Wolfgang, Christopher L. ; Schulick, Richard D. ; Lin, Ming Tseh ; Eshleman, James R. ; Hruban, Ralph H. ; Maitra, Anirban ; Matthaei, Hanno. / Loss of expression of the SWI/SNF chromatin remodeling subunit BRG1/SMARCA4 is frequently observed in intraductal papillary mucinous neoplasms of the pancreas. In: Human Pathology. 2012 ; Vol. 43, No. 4. pp. 585-591.
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abstract = "A better molecular characterization of intraductal papillary mucinous neoplasm (IPMN), the most frequent cystic precursor lesion of pancreatic adenocarcinoma, may have a pivotal role in its early detection and in the development of effective therapeutic strategies. BRG1, a central component of the chromatin remodeling complex SWI/SNF regulating transcription, is inactive in several malignancies. In this study, we evaluate the Brg1 expression in intraductal papillary mucinous neoplasm to better understand its role in the pancreatic carcinogenesis. Tissue microarrays of 66 surgically resected IPMNs were immunolabeled for the Brg1 protein. Expression patterns were then correlated with clinicopathologic parameters. Normal pancreatic epithelium strongly immunolabeled for Brg1. Reduced Brg1 expression was observed in 32 (53.3{\%}) of the 60 evaluable IPMN lesions and occurred more frequently in high-grade IPMNs (13 of 17 showed loss; 76{\%}) compared to intermediate-grade (15 of 29 showed loss; 52{\%}) and low-grade IPMNs (4 of 14 showed loss; 28{\%}) (P =.03). A complete loss of Brg1 expression was observed in 5 (8.3{\%}) of the 60 lesions. Finally, a decrease in Brg1 protein expression was furthermore found in a low-passage noninvasive IPMN cell line by Western blot analysis. We did not observe correlation between Brg1 expression and IPMN subtype or with location of the cyst. We provide first evidence that Brg1 expression is lost in noninvasive cystic precursor lesions of pancreatic adenocarcinoma.",
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AU - Dal Molin, Marco

AU - Hong, Seung Mo

AU - Hebbar, Sachidanand

AU - Sharma, Rajni

AU - Scrimieri, Francesca

AU - De Wilde, Roeland F.

AU - Mayo, Skye

AU - Goggins, Michael

AU - Wolfgang, Christopher L.

AU - Schulick, Richard D.

AU - Lin, Ming Tseh

AU - Eshleman, James R.

AU - Hruban, Ralph H.

AU - Maitra, Anirban

AU - Matthaei, Hanno

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N2 - A better molecular characterization of intraductal papillary mucinous neoplasm (IPMN), the most frequent cystic precursor lesion of pancreatic adenocarcinoma, may have a pivotal role in its early detection and in the development of effective therapeutic strategies. BRG1, a central component of the chromatin remodeling complex SWI/SNF regulating transcription, is inactive in several malignancies. In this study, we evaluate the Brg1 expression in intraductal papillary mucinous neoplasm to better understand its role in the pancreatic carcinogenesis. Tissue microarrays of 66 surgically resected IPMNs were immunolabeled for the Brg1 protein. Expression patterns were then correlated with clinicopathologic parameters. Normal pancreatic epithelium strongly immunolabeled for Brg1. Reduced Brg1 expression was observed in 32 (53.3%) of the 60 evaluable IPMN lesions and occurred more frequently in high-grade IPMNs (13 of 17 showed loss; 76%) compared to intermediate-grade (15 of 29 showed loss; 52%) and low-grade IPMNs (4 of 14 showed loss; 28%) (P =.03). A complete loss of Brg1 expression was observed in 5 (8.3%) of the 60 lesions. Finally, a decrease in Brg1 protein expression was furthermore found in a low-passage noninvasive IPMN cell line by Western blot analysis. We did not observe correlation between Brg1 expression and IPMN subtype or with location of the cyst. We provide first evidence that Brg1 expression is lost in noninvasive cystic precursor lesions of pancreatic adenocarcinoma.

AB - A better molecular characterization of intraductal papillary mucinous neoplasm (IPMN), the most frequent cystic precursor lesion of pancreatic adenocarcinoma, may have a pivotal role in its early detection and in the development of effective therapeutic strategies. BRG1, a central component of the chromatin remodeling complex SWI/SNF regulating transcription, is inactive in several malignancies. In this study, we evaluate the Brg1 expression in intraductal papillary mucinous neoplasm to better understand its role in the pancreatic carcinogenesis. Tissue microarrays of 66 surgically resected IPMNs were immunolabeled for the Brg1 protein. Expression patterns were then correlated with clinicopathologic parameters. Normal pancreatic epithelium strongly immunolabeled for Brg1. Reduced Brg1 expression was observed in 32 (53.3%) of the 60 evaluable IPMN lesions and occurred more frequently in high-grade IPMNs (13 of 17 showed loss; 76%) compared to intermediate-grade (15 of 29 showed loss; 52%) and low-grade IPMNs (4 of 14 showed loss; 28%) (P =.03). A complete loss of Brg1 expression was observed in 5 (8.3%) of the 60 lesions. Finally, a decrease in Brg1 protein expression was furthermore found in a low-passage noninvasive IPMN cell line by Western blot analysis. We did not observe correlation between Brg1 expression and IPMN subtype or with location of the cyst. We provide first evidence that Brg1 expression is lost in noninvasive cystic precursor lesions of pancreatic adenocarcinoma.

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KW - Pancreatic cancer

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