Page 12 - AAOMP Meeting 2019

Monday, June 10 - 8:00 am
COMPREHENSIVE GENOMIC ANALYSIS IDENTIfiES HIGH PREVALENCE OF PTCH1 MUTATIONS AND
CDK4 AMPLIfiCATION IN AGGRESSIVE KERATOCYSTIC ODONTOGENIC TUMORS
Mr. Macarius Abdelsayed (Augusta University, Dental College of Georgia), Dr. Rafik Abdelsayed
(Augusta University, Dental College of Georgia), Dr. Ravindra Kolhe (Augusta University, School of
Medicine)
Introduction: PTCH1 gene mutation is the etiology of KCOT, Gorlin syndrome and basal cell carcinoma.
Clinically, KCOT demonstrates a range of biological behavior. Some KCOTs are small, and indolent; while
others exhibit aggres-sive behavior with extensive bone destruction. The intent of this study is to report on
DNA sequencing of 8 cases of KCOTs, and demonstrate the genomic profiles that distinguish between
aggressive and indolent lesions. Method & Materials:8 KCOTs were selected from the archives of
institutional surgical pathology, and were further classified into 2 groups. Group 1) 4 cases, all males, 3
mandible, 1 maxilla that were ≤2cm radiolucencies, asymptomatic, or discovered on routine radiographic
examination. Group 2) 4 cases, 3 males, 1 female, all in mandible, and radio-graphically ≥5cm radiolucencies.
Next-generation sequencing (NGS) targeted 170 cancer genes including PTCH1 & others was performed on
sporadic KCOTs. DNA/RNA [T1] samples were retrieved from KCOTs for sequencing on a NGS platform.
The variant and fusion calls were recorded and interpreted on software provided by Illumina & IBM.
Results:The 4 KCOTs of group 1 exhibited PTCH1 alterations, including missense, nonsense, frameshift, and
splice site mutations. The 4 KCOTs of group 2 also exhibited PTCH1 alterations as seen in group 1.
Additionally, CDK4 amplification was found in 3 of the 4 cases in this group. Conclusions: All KCOTs
showed PTCH1 mutations in contrast to previously reported 30% in sporadic KCOTs. Genetic profiling in this
study seems to identify two biologically distinct groups of KCOTs, aggressive and indolent. Amplification of
CDK4 was noted in 75% of KCOTs in group 2 which demonstrated clinically aggressive behavior. The
coexistence of PTCH1 mutation and CDK4 amplification may exert a synergistic action to promote aggressive
behavior of some KCOTs. PTCH1 mutation and CDK4 amplification may provide a rational target for
bioavailable antiproliferative drugs.

Monday, June 10 - 8:12 am
EVALUATING NOD2 IN ORAL CROHN DISEASE USING FLUORESCENCE IN SITU
HYBRIDIZATION
Dr. Rekha Reddy (University of Florida College of Dentistry), Dr. Elizabeth A Bilodeau (University of
Pittsburgh School of Dental Medicine), Dr. Nadim Islam (University of Florida College of Dentistry), Dr.
Indraneel Bhattacharyya (University of Florida College of Dentistry), Dr. Donald Cohen (University of
Florida College of Dentistry), Dr. Sarah Fitzpatrick (University of Florida College of Dentistry), Dr.
Paras Patel (Texas A&M University College of Dentistry)
Introduction:Crohn disease (CD) is an inflammatory bowel disease that can affect any part of the
gastrointestinal (GI) tract. Familial clustering of cases and twin studies have suggested a genetic contribution
to the etiology of CD. NOD2 on chromosome 16 is the first gene to be associated with CD susceptibility. Oral
manifestations of CD are well- documented and may precede GI lesions in up to 40% of cases, especially in
children. The purpose of this study is to investigate if an amplification or deletion of the NOD2gene can be
detected using fluorescence in situ hybridization (FISH) analysis in oral biopsies of patients with a
confirmed diagnosis of CD.
Materials and Methods:An IRB-approved retrospective search for CD, pyostomatitis vegetans, and chronic
granulomatous stomatitis was performed within the archives of the University of Florida (UF), Texas A&M
University (TAMU), and the University of Pittsburgh (Pitt) oral pathology biopsy services between the years
1994-2018. Cases of patients who did not have a confirmed diagnosis of CD were excluded. Tissue blocks and
slides from 17 patients were retrieved. Unstained sections of each case were sent to the University of
Pittsburgh Medical Center for FISH analysis. The ratio of NOD2 and chromosome 16 control (CEP16) signals
was calculated for each case.
Results:The ratio of the NOD2 and CEP16 signals ranged from 0.95 to 1.57, with an average ratio of
1.08.
Conclusion:Neither amplification nor deletion of NOD2was identified in oral lesions of patients who have a
history of CD. Evaluation of additional genetic markers that have been implicated in CD and employing
further research to identify a reliable ancillary test that distinguishes oral granulomatous inflammation due to
CD is warranted.