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.
authors.affiliation: Mayo Clinic College of Medicine, Scottsdale, Arizona, USA.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Sekulic
authors.forename: Su Y
authors.initials: SY
authors.lastname: Kim
authors.forename: Galen
authors.initials: G
authors.lastname: Hostetter
authors.forename: Stephanie
authors.initials: S
authors.lastname: Savage
authors.forename: Janine G
authors.initials: JG
authors.lastname: Einspahr
authors.forename: Anil
authors.initials: A
authors.lastname: Prasad
authors.forename: Paul
authors.initials: P
authors.lastname: Sagerman
authors.forename: Clara
authors.initials: C
authors.lastname: Curiel-Lewandrowski
authors.forename: Robert
authors.initials: R
authors.lastname: Krouse
authors.forename: G Timothy
authors.initials: GT
authors.lastname: Bowden
authors.forename: James
authors.initials: J
authors.lastname: Warneke
authors.forename: David S
authors.initials: DS
authors.lastname: Alberts
authors.forename: Mark R
authors.initials: MR
authors.lastname: Pittelkow
authors.forename: David
authors.initials: D
authors.lastname: DiCaudo
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nickoloff
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Trent
authors.forename: Michael
authors.initials: M
authors.lastname: Bittner
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D055028:Comparative Genomic Hybridization; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D000072181:Inositol Polyphosphate 5-Phosphatases; D020411:Oligonucleotide Array Sequence Analysis; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D010744:Phosphoric Monoester Hydrolases; C000606429:INPP5A protein, human; D000072181:Inositol Polyphosphate 5-Phosphatases