# Functional characterization of 2q22.1 deletion in oral squamous cell carcinoma

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $53,494

## Abstract

PROJECT SUMMARY/ABSTRACT
Oral squamous cell carcinoma (OSCC) affects approximately 350,000 patients worldwide. The primary causes
of OSCC include smoking, consumption of alcoholic beverages, and infections with high-risk human
papillomaviruses (HPV). Currently, the main therapeutic modalities offered to patients include surgery, radiation,
chemotherapy, and immunotherapy. Despite the existing clinical interventions, the mortality for this disease
remains approximately 20% and is greater for higher grade tumors. OSCC tumors are genetically heterogenous
with a high rate of point mutations and somatic copy number variations (CNVs). Similar CNV patterns are
commonly observed in other squamous cell carcinomas such as those arising from the lung, cervix, and
esophagus. The CNVs also have a high propensity for co-occurring with inactivating mutations of tumor
suppressor genes. However, despite discoveries documenting the presence of various genomic loci undergoing
copy number alterations, the mechanistic contributions of these CNVs to OSCC carcinogenesis have yet to be
determined. The early and most frequent genetic alterations in OSCC include loss of tumor suppressors
CDKN2A (residing at 9p) in conjunction with mutations in TP53 (residing at 17p). Additionally, one of the most
commonly deleted sites within OSCC tumors is located at 2q22.1. This deletion is entirely contained within the
low-density lipoprotein receptor-related protein 1B gene, LRP1B, which has been implicated as a tumor
suppressor in other cancers but has not been characterized in OSCC. Although deletions at this locus occur
more frequently than would be expected by chance, inactivating point mutations within this gene are not common.
Moreover, LRP1B is not expressed in oral keratinocytes, raising the question as to why the deletions at this locus
occur at such a high frequency, despite the lack of gene expression. This suggests these deletions act by a
mechanism that is independent of interfering with LRP1B function. Therefore, I hypothesize that chromosomal
deletions at 2q22.1 act as driver events in OSCC progression via alteration of intragenic elements that
function in tumor suppression. This proposal will address my hypothesis via three specific aims: 1) Determine
the impact of 2q22.1 chromosomal deletions on the tumorigenic behavior of keratinocytes in vitro, 2) Identify
mechanisms downstream of 2q22.1 deletion responsible for tumorigenic behavior, and 3) Identify the minimal
critical region responsible for the observed phenotypic changes. These aims will be achieved utilizing a
combination of biochemical and molecular biology techniques to create the deletions observed in patient samples
in wild type keratinocytes and assess their contribution to tumorigenic behavior. Outcomes from this investigation
will be used in the development of novel therapeutic applications for suppression of OSCC and potentially various
other cancers that originate from the squamous epithelium.

## Key facts

- **NIH application ID:** 10669010
- **Project number:** 5F30DE029989-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Ramin Farhad
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $53,494
- **Award type:** 5
- **Project period:** 2020-09-02 → 2024-09-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10669010

## Citation

> US National Institutes of Health, RePORTER application 10669010, Functional characterization of 2q22.1 deletion in oral squamous cell carcinoma (5F30DE029989-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10669010. Licensed CC0.

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