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Risk Stratification of Oral Potentially Malignant Disorders in Fanconi Anemia Patients Using Autofluorescence Imaging and Cytology-On-A Chip Assay
- Source :
- Translational Oncology, Vol 11, Iss 2, Pp 477-486 (2018)
- Publication Year :
- 2018
- Publisher :
- Elsevier, 2018.
-
Abstract
- Fanconi anemia (FA) is a hereditary genomic instability disorder with a predisposition to leukemia and oral squamous cell carcinomas (OSCCs). Hematopoietic stem cell transplantation (HSCT) facilitates cure of bone marrow failure and leukemia and thus extends life expectancy in FA patients; however, survival of hematologic malignancies increases the risk of OSCC in these patients. We developed a "cytology-on-a-chip" (COC)-based brush biopsy assay for monitoring patients with oral potentially malignant disorders (OPMDs). Using this COC assay, we measured and correlated the cellular morphometry and Minichromosome Maintenance Complex Component 2 (MCM2) expression levels in brush biopsy samples of FA patients' OPMD with clinical risk indicators such as loss of autofluorescence (LOF), HSCT status, and mutational profiles identified by next-generation sequencing. Statistically significant differences were found in several cytology measurements based on high-risk indicators such as LOF-positive and HSCT-positive status, including greater variation in cell area and chromatin distribution, higher MCM2 expression levels, and greater numbers of white blood cells and cells with enlarged nuclei. Higher OPMD risk scores were associated with differences in the frequency of nuclear aberrations and differed based on LOF and HSCT statuses. We identified mutation of FAT1 gene in five and NOTCH-2 and TP53 genes in two cases of FA patients' OPMD. The high-risk OPMD of a non-FA patient harbored FAT1, CASP8, and TP63 mutations. Use of COC assay in combination with visualization of LOF holds promise for the early diagnosis of high-risk OPMD. These minimally invasive diagnostic tools are valuable for long-term surveillance of OSCC in FA patients and avoidance of unwarranted scalpel biopsies.
- Subjects :
- 0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
medicine.medical_treatment
Hematopoietic stem cell transplantation
lcsh:RC254-282
03 medical and health sciences
0302 clinical medicine
Fanconi anemia
Cytology
Internal medicine
TP63
medicine
business.industry
Bone marrow failure
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
3. Good health
Leukemia
Autofluorescence
030104 developmental biology
030220 oncology & carcinogenesis
business
FAT1
Subjects
Details
- Language :
- English
- ISSN :
- 19365233
- Volume :
- 11
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Translational Oncology
- Accession number :
- edsair.doi.dedup.....0d318b599c5837d0633c5a9c91c607c3