title: High resolution ArrayCGH and expression profiling identifies PTPRD and PCDH17/PCH68 as tumor suppressor gene candidates in laryngeal squamous cell carcinoma.
abstract: Many classical tumor suppressor genes (TSG) were identified by delineation of bi-allelic losses called homozygous deletions. To identify systematically homozygous deletions in laryngeal squamous cell carcinoma (LSCC) and to unravel novel putative tumor suppressor genes, we screened 10 LSCC cell lines using high resolution array comparative genomic hybridization (arrayCGH) and array based expression analysis. ArrayCGH identified altogether 113 regions harboring protein coding genes that showed strong reduction in copy number indicating a potential homozygous deletion. Out of the 113 candidate regions, 22 novel homozygous deletions that affected the coding sequences of 15 genes were confirmed by multiplexPCR. Three genes were homozygously lost in two cell lines: PCDH17/PCH68, PRR20, and PTPRD. For the 15 homozygously deleted genes, four showed statistically significant downregulation of expression in LSCC cell lines as compared with normal human laryngeal controls. These were ATG7 (1/10 cell line), ZMYND11 (BS69) (1/10 cell line), PCDH17/PCH68 (9/10 cell lines), and PTPRD (7/10 cell lines). Quantitative real-time PCR was used to confirm the downregulation of the candidate genes in 10 expression array-studied cell lines and an additional cohort of cell lines; statistical significant downregulation of PCDH17/PCH68 and PTPRD was observed. In line with this also Western blot analyses demonstrated a complete absence of the PCDH17 and PTPRD proteins. Thus, expression profiling confirmed recurrent alterations of two genes identified primarily by delineation of homozygous deletions. These were PCDH17/PCH68, the protocadherin gene, and the STAT3 inhibiting receptor protein tyrosine phosphatase gene PTPRD. These genes are good candidates for novel TSG in LSCC.
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. giefingm@man.poznan.pl
authors.forename: Maciej
authors.initials: M
authors.lastname: Giefing
authors.forename: Natalia
authors.initials: N
authors.lastname: Zemke
authors.forename: Damian
authors.initials: D
authors.lastname: Brauze
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kostrzewska-Poczekaj
authors.forename: Magdalena
authors.initials: M
authors.lastname: Luczak
authors.forename: Marcin
authors.initials: M
authors.lastname: Szaumkessel
authors.forename: Kinga
authors.initials: K
authors.lastname: Pelinska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kiwerska
authors.forename: Holger
authors.initials: H
authors.lastname: Tönnies
authors.forename: Reidar
authors.initials: R
authors.lastname: Grenman
authors.forename: Marek
authors.initials: M
authors.lastname: Figlerowicz
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Szyfter
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Jarmuz
mesh_terms: D015820:Cadherins / Q000235:genetics* / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D055028:Comparative Genomic Hybridization; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics* / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D015820:Cadherins; C529349:PCDH17 protein, human; C090899:PTPRD protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2