Loss of inositol polyphosphate 5-phosphatase is an early event in development of cutaneous squamous cell carcinoma

Aleksandar Sekulic, Su Y. Kim, Galen Hostetter, Stephanie Savage, Janine G Einspahr, Anil P Rama Rao, Paul Sagerman, Clara N Curiel, Robert S Krouse, G. Timothy Bowden, James A Warneke, David S Alberts, Mark R. Pittelkow, David DiCaudo, Brian J. Nickoloff, Jeffrey M. Trent, Michael Bittner

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Cutaneous squamous cell carcinoma (SCC) occurs commonly and can metastasize. Identification of specific molecular aberrations and mechanisms underlying the development and progression of cutaneous SCC may lead to better prognostic and therapeutic approaches and more effective chemoprevention strategies. To identify genetic changes associated with early stages of cutaneous SCC development, we analyzed a series of 40 archived skin tissues ranging from normal skin to invasive SCC. Using high-resolution array-based comparative genomic hybridization, we identified deletions of a region on chromosome 10q harboring the INPP5A gene in 24% of examined SCC tumors. Subsequent validation by immunohistochemistry on an independent sample set of 71 SCC tissues showed reduced INPP5A protein levels in 72% of primary SCC tumors. Decrease in INPP5A protein levels seems to be an early event in SCC development, as it also is observed in 9 of 26 (35%) examined actinic keratoses, the earliest stage in SCC development. Importantly, further reduction of INPP5A levels is seen in a subset of SCC patients as the tumor progresses from primary to metastatic stage. The observed frequency and pattern of loss indicate that INPP5A, a negative regulator of inositol signaling, may play a role in development and progression of cutaneous SCC tumors.

Original languageEnglish (US)
Pages (from-to)1277-1283
Number of pages7
JournalCancer Prevention Research
Volume3
Issue number10
DOIs
StatePublished - Oct 2010

Fingerprint

Squamous Cell Carcinoma
Skin
Neoplasms
Inositol Polyphosphate 5-Phosphatases
Actinic Keratosis
Comparative Genomic Hybridization
Chemoprevention
Inositol
Proteins
Chromosomes
Immunohistochemistry

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Loss of inositol polyphosphate 5-phosphatase is an early event in development of cutaneous squamous cell carcinoma. / Sekulic, Aleksandar; Kim, Su Y.; Hostetter, Galen; Savage, Stephanie; Einspahr, Janine G; Rama Rao, Anil P; Sagerman, Paul; Curiel, Clara N; Krouse, Robert S; Bowden, G. Timothy; Warneke, James A; Alberts, David S; Pittelkow, Mark R.; DiCaudo, David; Nickoloff, Brian J.; Trent, Jeffrey M.; Bittner, Michael.

In: Cancer Prevention Research, Vol. 3, No. 10, 10.2010, p. 1277-1283.

Research output: Contribution to journalArticle

Sekulic, A, Kim, SY, Hostetter, G, Savage, S, Einspahr, JG, Rama Rao, AP, Sagerman, P, Curiel, CN, Krouse, RS, Bowden, GT, Warneke, JA, Alberts, DS, Pittelkow, MR, DiCaudo, D, Nickoloff, BJ, Trent, JM & Bittner, M 2010, 'Loss of inositol polyphosphate 5-phosphatase is an early event in development of cutaneous squamous cell carcinoma', Cancer Prevention Research, vol. 3, no. 10, pp. 1277-1283. https://doi.org/10.1158/1940-6207.CAPR-10-0058
Sekulic, Aleksandar ; Kim, Su Y. ; Hostetter, Galen ; Savage, Stephanie ; Einspahr, Janine G ; Rama Rao, Anil P ; Sagerman, Paul ; Curiel, Clara N ; Krouse, Robert S ; Bowden, G. Timothy ; Warneke, James A ; Alberts, David S ; Pittelkow, Mark R. ; DiCaudo, David ; Nickoloff, Brian J. ; Trent, Jeffrey M. ; Bittner, Michael. / Loss of inositol polyphosphate 5-phosphatase is an early event in development of cutaneous squamous cell carcinoma. In: Cancer Prevention Research. 2010 ; Vol. 3, No. 10. pp. 1277-1283.
@article{9fb5ca635fb743358e607caffb19be82,
title = "Loss of inositol polyphosphate 5-phosphatase is an early event in development of cutaneous squamous cell carcinoma",
abstract = "Cutaneous squamous cell carcinoma (SCC) occurs commonly and can metastasize. Identification of specific molecular aberrations and mechanisms underlying the development and progression of cutaneous SCC may lead to better prognostic and therapeutic approaches and more effective chemoprevention strategies. To identify genetic changes associated with early stages of cutaneous SCC development, we analyzed a series of 40 archived skin tissues ranging from normal skin to invasive SCC. Using high-resolution array-based comparative genomic hybridization, we identified deletions of a region on chromosome 10q harboring the INPP5A gene in 24{\%} of examined SCC tumors. Subsequent validation by immunohistochemistry on an independent sample set of 71 SCC tissues showed reduced INPP5A protein levels in 72{\%} of primary SCC tumors. Decrease in INPP5A protein levels seems to be an early event in SCC development, as it also is observed in 9 of 26 (35{\%}) examined actinic keratoses, the earliest stage in SCC development. Importantly, further reduction of INPP5A levels is seen in a subset of SCC patients as the tumor progresses from primary to metastatic stage. The observed frequency and pattern of loss indicate that INPP5A, a negative regulator of inositol signaling, may play a role in development and progression of cutaneous SCC tumors.",
author = "Aleksandar Sekulic and Kim, {Su Y.} and Galen Hostetter and Stephanie Savage and Einspahr, {Janine G} and {Rama Rao}, {Anil P} and Paul Sagerman and Curiel, {Clara N} and Krouse, {Robert S} and Bowden, {G. Timothy} and Warneke, {James A} and Alberts, {David S} and Pittelkow, {Mark R.} and David DiCaudo and Nickoloff, {Brian J.} and Trent, {Jeffrey M.} and Michael Bittner",
year = "2010",
month = "10",
doi = "10.1158/1940-6207.CAPR-10-0058",
language = "English (US)",
volume = "3",
pages = "1277--1283",
journal = "Cancer Prevention Research",
issn = "1940-6207",
publisher = "American Association for Cancer Research Inc.",
number = "10",

}

TY - JOUR

T1 - Loss of inositol polyphosphate 5-phosphatase is an early event in development of cutaneous squamous cell carcinoma

AU - Sekulic, Aleksandar

AU - Kim, Su Y.

AU - Hostetter, Galen

AU - Savage, Stephanie

AU - Einspahr, Janine G

AU - Rama Rao, Anil P

AU - Sagerman, Paul

AU - Curiel, Clara N

AU - Krouse, Robert S

AU - Bowden, G. Timothy

AU - Warneke, James A

AU - Alberts, David S

AU - Pittelkow, Mark R.

AU - DiCaudo, David

AU - Nickoloff, Brian J.

AU - Trent, Jeffrey M.

AU - Bittner, Michael

PY - 2010/10

Y1 - 2010/10

N2 - Cutaneous squamous cell carcinoma (SCC) occurs commonly and can metastasize. Identification of specific molecular aberrations and mechanisms underlying the development and progression of cutaneous SCC may lead to better prognostic and therapeutic approaches and more effective chemoprevention strategies. To identify genetic changes associated with early stages of cutaneous SCC development, we analyzed a series of 40 archived skin tissues ranging from normal skin to invasive SCC. Using high-resolution array-based comparative genomic hybridization, we identified deletions of a region on chromosome 10q harboring the INPP5A gene in 24% of examined SCC tumors. Subsequent validation by immunohistochemistry on an independent sample set of 71 SCC tissues showed reduced INPP5A protein levels in 72% of primary SCC tumors. Decrease in INPP5A protein levels seems to be an early event in SCC development, as it also is observed in 9 of 26 (35%) examined actinic keratoses, the earliest stage in SCC development. Importantly, further reduction of INPP5A levels is seen in a subset of SCC patients as the tumor progresses from primary to metastatic stage. The observed frequency and pattern of loss indicate that INPP5A, a negative regulator of inositol signaling, may play a role in development and progression of cutaneous SCC tumors.

AB - Cutaneous squamous cell carcinoma (SCC) occurs commonly and can metastasize. Identification of specific molecular aberrations and mechanisms underlying the development and progression of cutaneous SCC may lead to better prognostic and therapeutic approaches and more effective chemoprevention strategies. To identify genetic changes associated with early stages of cutaneous SCC development, we analyzed a series of 40 archived skin tissues ranging from normal skin to invasive SCC. Using high-resolution array-based comparative genomic hybridization, we identified deletions of a region on chromosome 10q harboring the INPP5A gene in 24% of examined SCC tumors. Subsequent validation by immunohistochemistry on an independent sample set of 71 SCC tissues showed reduced INPP5A protein levels in 72% of primary SCC tumors. Decrease in INPP5A protein levels seems to be an early event in SCC development, as it also is observed in 9 of 26 (35%) examined actinic keratoses, the earliest stage in SCC development. Importantly, further reduction of INPP5A levels is seen in a subset of SCC patients as the tumor progresses from primary to metastatic stage. The observed frequency and pattern of loss indicate that INPP5A, a negative regulator of inositol signaling, may play a role in development and progression of cutaneous SCC tumors.

UR - http://www.scopus.com/inward/record.url?scp=77958532146&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77958532146&partnerID=8YFLogxK

U2 - 10.1158/1940-6207.CAPR-10-0058

DO - 10.1158/1940-6207.CAPR-10-0058

M3 - Article

VL - 3

SP - 1277

EP - 1283

JO - Cancer Prevention Research

JF - Cancer Prevention Research

SN - 1940-6207

IS - 10

ER -