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Abstract 1852: Multiple PI3K pathway mutations predominate in low stage endometrial carcinomas

Publication ,  Conference
Roque, DR; Jeck, WR; Hayes, DN; Dizon, AM; Clark, L; Pierce, S; Wysham, WZ; Castellano, T; Gehrig, PA; Bae-Jump, V
Published in: Cancer Research
July 15, 2016

Objectives: Endometrial cancers (ECs) frequently harbor mutations in PI3K pathway genes. Our objective was to determine the mutation frequency of the PIK3 pathway in the tumors of EC patients prospectively enrolled on an IRB-approved institutional tumor sequencing initiative (UNCseq) and correlate these with clinical factors.Methods: Snap-frozen and FFPE tissue samples were collected from patients enrolled on UNCseq (NCT01457196). DNA was isolated using the Puregene DNA purification system, and Illumina libraries were prepared separately from tumor and a matched normal sample from each patient. Relevant targets, were enriched by a custom designed Agilent SureSelect hybrid capture enrichment library using standard protocols. Samples were sequenced on Illumina HiSeq machines in a variety of formats. Statistical analysis of clinical correlates was performed in R (v 3.1.1).Results: Data was collected from 109 EC patients. Thirty-six tumors (33.0%), 34 of which were endometrioid, had >2 mutations between PIK3CA and PIK3R1. 20 patients had multiple PIK3CA mutations (18.3%) and 11 had multiple PIK3R1 mutations (10.1%). In all but 5 cases, multiple mutations of PIK3R1 or PIK3CA were coincident with PTEN mutation (p = 0.018). There were strong correlations between PI3K pathway mutations and tumor grade and stage. High stage tumors (stage >2) were less likely (5/36) than stage 1 tumors (31/73) to have multiple PI3K mutations (p = 0.0056). Though not reaching significance, grade 3 tumors (8/37) were less likely than low-grade tumors (28/72) to demonstrate multiple PI3K mutations (p = 0.11). Of the 10 serous ECs, none exhibited multiple PI3K mutations.Conclusions: There is a strong relationship between mutated PIK3 pathway genes and clinically relevant tumor biology in ECs. Multiple mutations in the PIK3 pathway are common, suggesting that PI3K pathway inhibition in EC may need to be directed against PIK3CA and PIK3R1 simultaneously. These multiply mutated tumors are strongly linked to lower stage and grade tumors with concurrent PTEN mutations. We posit that initially PTEN mutant clones may give rise to subclonal populations with various PI3K mutations which may be relatively indolent until additional driver mutations are acquired such that one subpopulation predominates, resulting in higher grade and stage ECs.Citation Format: Dario R. Roque, Will R. Jeck, David N. Hayes, Arthur M. Dizon, Leslie Clark, Stuart Pierce, Weiya Z. Wysham, Tara Castellano, Paola A. Gehrig, Victoria Bae-Jump. Multiple PI3K pathway mutations predominate in low stage endometrial carcinomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1852.

Duke Scholars

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

July 15, 2016

Volume

76

Issue

14_Supplement

Start / End Page

1852 / 1852

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

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MLA
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Roque, D. R., Jeck, W. R., Hayes, D. N., Dizon, A. M., Clark, L., Pierce, S., … Bae-Jump, V. (2016). Abstract 1852: Multiple PI3K pathway mutations predominate in low stage endometrial carcinomas. In Cancer Research (Vol. 76, pp. 1852–1852). American Association for Cancer Research (AACR). https://doi.org/10.1158/1538-7445.am2016-1852
Roque, Dario R., Will R. Jeck, David N. Hayes, Arthur M. Dizon, Leslie Clark, Stuart Pierce, Weiya Z. Wysham, Tara Castellano, Paola A. Gehrig, and Victoria Bae-Jump. “Abstract 1852: Multiple PI3K pathway mutations predominate in low stage endometrial carcinomas.” In Cancer Research, 76:1852–1852. American Association for Cancer Research (AACR), 2016. https://doi.org/10.1158/1538-7445.am2016-1852.
Roque DR, Jeck WR, Hayes DN, Dizon AM, Clark L, Pierce S, et al. Abstract 1852: Multiple PI3K pathway mutations predominate in low stage endometrial carcinomas. In: Cancer Research. American Association for Cancer Research (AACR); 2016. p. 1852–1852.
Roque, Dario R., et al. “Abstract 1852: Multiple PI3K pathway mutations predominate in low stage endometrial carcinomas.” Cancer Research, vol. 76, no. 14_Supplement, American Association for Cancer Research (AACR), 2016, pp. 1852–1852. Crossref, doi:10.1158/1538-7445.am2016-1852.
Roque DR, Jeck WR, Hayes DN, Dizon AM, Clark L, Pierce S, Wysham WZ, Castellano T, Gehrig PA, Bae-Jump V. Abstract 1852: Multiple PI3K pathway mutations predominate in low stage endometrial carcinomas. Cancer Research. American Association for Cancer Research (AACR); 2016. p. 1852–1852.

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

July 15, 2016

Volume

76

Issue

14_Supplement

Start / End Page

1852 / 1852

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis