Case Report: Detection of TP53 (17p13) Deletion in a Patient with Suspected B-Cell Non-Hodgkin Lymphoma Using Fluorescence In-Situ Hybridization (FISH)

By SWA

Abstract

We report a case of a patient with a suspected B-cell lymphoproliferative disorder in whom fluorescence in-situ hybridization (FISH) analysis revealed a monoallelic deletion of the TP53 locus at 17p13. This finding has significant prognostic and therapeutic implications, as TP53 deletions are associated with poor response to conventional therapies and more aggressive disease behavior in chronic lymphocytic leukemia (CLL) and other B-cell non-Hodgkin lymphomas (NHL). This case highlights the critical role of cytogenetic analysis in the diagnostic and therapeutic approach to B-cell malignancies.

Deletions at the TP53 locus in chromosome band 17p13 are found in a number of non-Hodgkin lymphomas (follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia) 

Introduction

Chromosomal abnormalities play a pivotal role in the pathogenesis, classification, and prognosis of B-cell lymphoproliferative disorders. Among these, deletions involving the TP53 gene at chromosome 17p13 are recognized as one of the most adverse prognostic markers, strongly correlating with treatment resistance and inferior survival outcomes in diseases such as CLL, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma. Fluorescence in-situ hybridization (FISH) remains a highly sensitive method for the detection of such abnormalities even in non-dividing (interphase) cells.

Case Presentation

A patient with clinical suspicion of a B-cell non-Hodgkin lymphoma underwent cytogenetic evaluation for prognostic stratification. Peripheral blood or bone marrow samples were subjected to FISH analysis following in vitro stimulation of the lymphocytes with DSP30/IL-2 to enrich for proliferating B-cells.

Materials and Methods

Sample Preparation

Lymphocyte cultures were stimulated with DSP30 and interleukin-2 (IL-2) for 72 hours to enhance mitotic activity. Interphase nuclei were harvested for FISH analysis.

FISH Probes and Targets

The following commercially available probe sets (Metasystems, Germany) were employed:

  1. XL ATM/TP53 Probe

    • TP53 (17p13)

    • ATM gene (11q22) 

  2. XL DLEU1/LAMP1/12cen Probe

    • DLEU1 (13q14.2)

    • LAMP1 (13q34)

    • 12cen (12p11.1–12q11.1)

  3. XL IGH BA Probe

    • IGH (14q32)

  4. XL 6421/6q23/6cen Probe

    • D6S1594 (6q23)

    • MYB (6q23.3)

    • D6Z1 (6p11.1-11)

These probes are designed to detect the most common chromosomal aberrations seen in CLL and other B-cell NHL subtypes.

Microscopy and Scoring

FISH signals were evaluated in 300 interphase nuclei for the ATM/TP53 probe and in 100–200 nuclei for the remaining probes, following standard laboratory protocols. Signal patterns were scored manually by experienced cytogeneticists.

Basic Laboratory Tests

These are often the first tests done:

TestPurpose
Complete Blood Count (CBC)Detects abnormal white cells, anemia, low platelets
Peripheral blood smearLooks at the shape and appearance of blood cells
Lactate dehydrogenase (LDH)Marker for cell turnover (often elevated)
Uric acidCan be elevated due to rapid cell breakdown
Electrolytes (Na, K, Ca, etc.)Assesses overall metabolic state
Liver and kidney function tests (ALT, AST, creatinine, BUN)Needed before treatment

Results

ATM/TP53 Probe (300 nuclei analyzed)

  • Normal diploid pattern (ATM×2, TP53×2): 263 nuclei (86.7%)

  • Deletion pattern (ATM×2, TP53×1): 37 nuclei (13.3%)

Other Probes

  • DLEU1/LAMP1/12cen (200 nuclei): diploid pattern observed in all nuclei.

  • IGH BA (100 nuclei): diploid pattern observed in all nuclei.

  • 6421/6q23/6cen (100 nuclei): diploid pattern observed in all nuclei.

No evidence of additional chromosomal aberrations (such as trisomy 12, del(13q14), MYB or IGH translocations) was identified.

Medications / Substances to Avoid or Be Careful With

Always talk to your doctor first. In many leukemia/lymphoma patients, especially when on treatment:

Medication/SubstanceWhy to avoid
NSAIDs (ibuprofen, naproxen, aspirin)Can increase bleeding risk (especially if platelets are low)
Herbal supplements (St. John’s Wort, etc.)May interfere with chemotherapy or targeted therapy
Grapefruit or grapefruit juiceCan affect how some medications are broken down (e.g. ibrutinib, venetoclax)
AlcoholCan stress the liver, worsen fatigue, or interfere with medications
Certain antibiotics or antifungalsMay interact with cancer medications

Why certain antibiotics or antifungals can be a problem:

Some antibiotics and antifungals affect how your body processes certain leukemia/lymphoma medications.
This mostly happens because of interactions with liver enzymes (CYP3A4 system), which break down many drugs.

If this system is blocked or overactivated, your cancer medicine may:

  • Build up to unsafe levels (more side effects)

  • Be broken down too fast (less effective)

Antifungals to be cautious with:

MedicationProblem
Fluconazole    Mild-to-moderate CYP3A4 inhibitor (can increase drug levels)
Itraconazole    Strong CYP3A4 inhibitor
Posaconazole    Strong CYP3A4 inhibitor
Voriconazole    Strong CYP3A4 inhibitor
Ketoconazole    Strong CYP3A4 inhibitor

Interpretation

The FISH analysis demonstrated the presence of a subclone (13.3% of analyzed nuclei) carrying a monoallelic deletion of the TP53 locus at 17p13, with no other chromosomal abnormalities detected in the analyzed loci. These findings confirm the presence of a pathological cell population with a high-risk genetic aberration.

Discussion

Pathophysiology and Clinical Significance of TP53 Deletion

The TP53 gene encodes a critical tumor suppressor protein involved in maintaining genomic stability by regulating cell cycle arrest, DNA repair, and apoptosis in response to genomic damage. Loss of TP53 function allows malignant cells to evade apoptosis and accumulate genetic errors, promoting clonal evolution and treatment resistance.

TP53 deletions and/or mutations are identified in approximately 5–10% of previously untreated CLL patients and up to 40% of relapsed or refractory cases. The presence of TP53 deletion is associated with:

  • Poor response to DNA-damaging chemotherapies (e.g., fludarabine, cyclophosphamide, bendamustine).

  • Shorter progression-free and overall survival.

  • Increased risk of transformation to more aggressive lymphoma subtypes (e.g., Richter transformation).

Therapeutic Implications

Based on current clinical guidelines, patients with TP53 deletion should be considered for alternative frontline therapies that do not rely on functional TP53-mediated apoptosis, including:

  • BTK inhibitors: Ibrutinib, Acalabrutinib, Zanubrutinib

  • BCL-2 inhibitors: Venetoclax (typically combined with CD20 antibodies such as Obinutuzumab)

  • PI3K inhibitors (in selected cases)

  • CAR-T cell therapy or allogeneic stem cell transplantation (in highly selected, refractory or high-risk patients)

Molecular analysis for co-existing TP53 mutations is recommended, as biallelic TP53 disruption (deletion plus mutation) carries an even more unfavorable prognosis.

Monitoring and Follow-Up

Patients with TP53 aberrations require more frequent disease monitoring due to the higher risk of disease progression and therapeutic resistance.

Conclusion

This case demonstrates the utility of interphase FISH for the detection of clinically significant chromosomal aberrations in B-cell lymphoproliferative disorders. The identification of TP53 deletion provides essential prognostic information and guides treatment planning towards targeted therapies that circumvent the loss of TP53 function.

Reference: 

ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia—2024 update
https://pmc.ncbi.nlm.nih.gov/articles/PMC11217004/

Patients with chronic lymphocytic leukaemia and clonal deletion of both 17p13.1 and 11q22.3 have a very poor prognosis https://pmc.ncbi.nlm.nih.gov/articles/PMC3907074/

 

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742

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