# 3q26 Amplified Genes as Cooperative Oncogenic Drivers of Lung Squamous Cell Carcinoma

> **NIH NIH R03** · MAYO CLINIC  JACKSONVILLE · 2020 · $78,250

## Abstract

PROJECT SUMMARY/ABSTRACT
3q26 copy number gains (CNGs) have been found to be present in both early stage pre-invasive lung
squamous cell lesions and in invasive lung squamous cell carcinomas (LSCCs). In addition, amplification
involving the 3q26 region is consistently observed in high-grade, and less frequently in low-grade pre-invasive
lesions. Furthermore, the presence of 3q26 amplification has been shown to accurately predict patients with
endobronchial squamous metaplastic and dysplastic lesions that subsequently progressed to lung cancer.
However, whether 3q26 CNG is an early oncogenic event that drives pre-neoplastic lesions to progress to
malignant LSCC has not been adequately explored. Our studies have demonstrated that at least 3 genes
(PRKCI, ECT2 and SOX2) on 3q26 are co-amplified and functionally collaborate in maintaining the
transformed phenotype of LSCC cells. Our preliminary data demonstrates that 1) loss of Trp53 and
overexpression of Sox2 induces expansion of mouse primary lung basal stem cells (LBSCs) ex vivo and
formation of tumors that harbor squamous cell lineage markers in vivo; 2) forced co-overexpression of PKCι,
Ect2 and Sox2 in Trp53 deficient mouse LBSCs further enhances expansion and causes morphological
transformation ex vivo; and 3) Trp53 deficient LBSCs co-overexpressing PKCι, Ect2 and Sox2 exhibit PKCι
mediated T328-Ect2 and T118-Sox2 phosphorylation. Based on these data, we hypothesize that PKCι, Ect2
and Sox2 are key oncogenic drivers of the 3q26 amplicon and together co-operate to mediate 3q26 CNG-
driven LSCC tumorigenesis. These hypotheses will be tested by completing two interrelated specific aims
designed to: 1) determine if PKCι, Ect2 and Sox2 co-operate in Trp53 deficient LBSC tumor formation in vivo
and 2) assess the role of PKCι-mediated Ect2 and Sox2 phosphorylation and downstream signaling in Trp53
deficient LBSC morphological transformation ex vivo and tumor initiation in vivo. Successful completion of
these aims will provide significant new insight into the role of multi-genic 3q26 amplification in LSCC
development and progression.

## Key facts

- **NIH application ID:** 9838734
- **Project number:** 5R03CA235189-02
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** Verline Justilien
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $78,250
- **Award type:** 5
- **Project period:** 2018-12-14 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9838734

## Citation

> US National Institutes of Health, RePORTER application 9838734, 3q26 Amplified Genes as Cooperative Oncogenic Drivers of Lung Squamous Cell Carcinoma (5R03CA235189-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9838734. Licensed CC0.

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