PeCan-Seq identifies ctDNA for pediatric cancers, showing high sensitivity in leukemias and limited detection in solid and brain tumors.

Circulating tumor DNA (ctDNA) analysis for cancer detection and monitoring is a noninvasive approach and has shown a great potential for its use in. However, its use in childhood cancers especially leukemia is limited research (1^✔ ✔Trusted Source
Genomic profiling of circulating tumor DNA for childhood cancers

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Development of PeCan-Seq

PeCan-Seq was developed as a deep sequencing method specifically for examining somatic genomic changes comprising nucleotide substitutions, CNVs, and pathogenic rearrangements that create oncogenic fusions.This method employs smaller plasma volumes (1 mL) to detect tumor derived DNA.

Plasma samples were collected at diagnosis from 233 children with various cancer types:

• Hematologic malignancies: 177 patients
• Solid tumors: 38 patients
• Brain tumors: 18 patients

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Key Findings in ctDNA Analysis for Childhood Cancers

ctDNA Detection Across Cancer Types

Hematologic Malignancies:

• ctDNA was detected in all the 177 patients (100%).
• Median ctDNA fraction: 0.77.
• PeCan-Seq identified 97% of 789 expected tumor variants.

Solid Tumors:
Blood ctDNA was identified in 19 of 38 patients (50%).

Brain Tumors:

ctDNA was identified in only one patient in the 18 patients with breast cancer (~5.5%).

Sensitivity and Correlation with Residual Disease

In patients with B-cell acute lymphoblastic leukemia (B-ALL):

• They also showed that ctDNA alterations are significantly associated with the levels of MRD detected by flow cytometry.
• The use of serial plasma sampling showed the application of ctDNA for the assessment of disease dynamic and therapeutic efficacy.

Multi-Tumor Detection

The feasibility of PeCan-Seq was established using simultaneously diagnosed B-ALL and neuroblastoma samples. These results of distinguished tumor-specific somatic variants in the plasmic sample of this individual patient demonstrate the high sensitivity of this method in multi-tumor profiling.

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Advantages of PeCan-Seq

Sensitivity:
Specific identification and detection of ctDNA changes, especially in hematologic neoplasms.
Specificity in detecting sequence mutations, CNVs and structural variations.

Non-Invasive Nature:

With the ability to use only 1 mL of plasma, there is a decreased demand for biopsying procedures.

Disease Monitoring:

A clinical correlation with MRD allows us to assess the effectiveness of the treatment and the return of the disease.

Challenges in Solid and Brain Tumors

• There was a detection of lower chances of ctDNA in solid tumors as well as the brain tumor possibly due to reduced release of ctDNA in the bloodstream.
• However, some additional enhancement is needed so as to achieve better detection sensitivity for such cancers.

PeCan-Seq is a highly sensitive and informative method for ctDNA molecular characterization in children with cancer, especially in hematologic neoplasms. The detection of heterogeneous somatic variants in minor plasma volumes is also indicative of its applications as a non-invasive diagnostic tool for disease. There is a certain success of this treatment strategy in hematologic cancers, therefore it is necessary to improve its effectiveness in solid and brain tumors.

Reference:

1. Genomic profiling of circulating tumor DNA for childhood cancers – (https://www.nature.com/articles/s41375-024-02461-x)

Source-Medindia