Molecular dissection of 17q12 amplicon in upper gastrointestinal adenocarcinomas

Nazif Maqani, Abbes Belkhiri, Christopher Moskaluk, Sakari Knuutila, Altaf A. Dar, Wael El-Rifai

Research output: Contribution to journalArticle

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Abstract

DNA amplification at 17q is frequently detected in upper gastrointestinal adenocarcinomas (UGC; stomach and esophagus). In this study, we did fluorescence in situ hybridization on a tissue microarray that contained 304 UGCs and 89 normal stomach samples using a ∼ 168-kb BAC clone (CTD-2019C10) that maps to 17q12-q21.1. This 168-kb region contains the following genes: PPP1R1B/DARPP-32, STARD3, TCAP, PNMT, PERLD1, ERBB2, C17orf37, and GRB7 as well as the first two exons of ZNFN1A3. DNA amplification (≥5 signals) was detected in 85 of 282 (30%) of UGCs, and high-level amplification (≥10 signals) was seen in 28 of 282 (10%) of all tumors. Adenocarcinomas of gastroesophageal junction and lower esophagus had the highest frequency of amplification (45%) compared with stomach tumors (27%; P = 0.04). On the other hand, 38% of tumors with intestinal-type morphology had amplification compared with 26% of diffuse-type tumors (P = 0.02). We further did quantitative real-time reverse transcription-PCR on 74 frozen tissue samples from UGCs for 11 genes located within or adjacent to the boundaries of this ∼ 168-kb genomic region. These genes include all 9 genes that are fully or partially located inside the CTD-2019C10 clone as well as 2 additional adjacent genes (NEUROD and TOP2A). Overexpression of PPP1R1B/DARPP-32, TCAP, and TOP2A was seen in approximately half of the tumors, whereas STARD3 and ZNFN1A3 were rarely overexpressed (12%). Interestingly, there was a statistical correlation between expression of all 8 genes that map between PPP1R1B/DARPP-32 and GRB7, whereas expression of NEUROD, ZNFN1A3, and TOP2A that are partially inside or adjacent to the boundaries of the CTD-2019C10 clone did not correlate with the expression of any of these 8 genes. These data show a transcriptionally active oncogenomic region bounded by PPP1R1B/DARPP-32 and GRB7 in UGCs and provide further insight into expression levels of several critical genes.

Original languageEnglish (US)
Pages (from-to)449-455
Number of pages7
JournalMolecular Cancer Research
Volume4
Issue number7
DOIs
StatePublished - Jul 1 2006
Externally publishedYes

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Dissection
Adenocarcinoma
Genes
Stomach
Clone Cells
Neoplasms
Esophagus
Esophagogastric Junction
DNA
Fluorescence In Situ Hybridization
Reverse Transcription
Exons
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Molecular dissection of 17q12 amplicon in upper gastrointestinal adenocarcinomas. / Maqani, Nazif; Belkhiri, Abbes; Moskaluk, Christopher; Knuutila, Sakari; Dar, Altaf A.; El-Rifai, Wael.

In: Molecular Cancer Research, Vol. 4, No. 7, 01.07.2006, p. 449-455.

Research output: Contribution to journalArticle

Maqani, Nazif ; Belkhiri, Abbes ; Moskaluk, Christopher ; Knuutila, Sakari ; Dar, Altaf A. ; El-Rifai, Wael. / Molecular dissection of 17q12 amplicon in upper gastrointestinal adenocarcinomas. In: Molecular Cancer Research. 2006 ; Vol. 4, No. 7. pp. 449-455.
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