WHOLE EXOME SEQUENCING OF RELAPSED PEDIATRIC T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA
(Abstract release date: 05/19/16)
EHA Library. Karrman K. 06/09/16; 134493; PB1593
Dr. Kristina Karrman
Contributions
Contributions
Abstract
Abstract: PB1593
Type: Publication Only
Background
Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood responsible for a quarter of all pediatric cancers. T-cell ALL (T-ALL) makes up 10-15% of childhood ALL. Close to 80% of children diagnosed with T-ALL survive the disease if treated according to standard protocols. However, one in five T-ALL patients relapse and for this group the outcome is very dismal, less than half of the patients are cured.
Aims
We undertook exome sequencing of matched diagnostic, remission and two relapse (relapse 1 and 2) DNA samples from a pediatric T-ALL patient.
Methods
Agilent SureSelect exome capture was used and each capture library was sequenced on the HiSeq2000 platform. >98% of the targets were sequenced with at least 20x coverage.
Results
In total, 66 somatic single nucleotide variants (SNVs) were detected in the three samples. Almost half of the SNVs detected at diagnosis were also seen at relapse 1 and/or 2 (7/15, 47%). This result hence indicates that the relapse evolves from a clone present at diagnosis. STAT5B mutations, including N642H, were recently implicated as a putative drivers of T-ALL. We identified the N642H mutations in a homozygous state in both diagnostic and relapse samples, further validating the role of STAT5B in T-cell leukemogenesis. Two separate NOTCH1 mutations were seen in minor subclones at diagnosis. Interestingly, these mutations were not seen in the relapse samples, however relapse 2 acquired a FBXW7 mutation which could render the leukemic cells renewed aberrant NOTCH1 activity. The vast majority of identified SNVs (51/66, 77%) were selectively seen in the relapsed samples. Notably, some relapse-specific mutations were detected in genes responsible for drug resistance; ABCA2 and NT5C2.
Conclusion
To elucidate genes involved in relapsed T-ALL could hopefully result in new targeted treatments.
Session topic: E-poster
Type: Publication Only
Background
Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood responsible for a quarter of all pediatric cancers. T-cell ALL (T-ALL) makes up 10-15% of childhood ALL. Close to 80% of children diagnosed with T-ALL survive the disease if treated according to standard protocols. However, one in five T-ALL patients relapse and for this group the outcome is very dismal, less than half of the patients are cured.
Aims
We undertook exome sequencing of matched diagnostic, remission and two relapse (relapse 1 and 2) DNA samples from a pediatric T-ALL patient.
Methods
Agilent SureSelect exome capture was used and each capture library was sequenced on the HiSeq2000 platform. >98% of the targets were sequenced with at least 20x coverage.
Results
In total, 66 somatic single nucleotide variants (SNVs) were detected in the three samples. Almost half of the SNVs detected at diagnosis were also seen at relapse 1 and/or 2 (7/15, 47%). This result hence indicates that the relapse evolves from a clone present at diagnosis. STAT5B mutations, including N642H, were recently implicated as a putative drivers of T-ALL. We identified the N642H mutations in a homozygous state in both diagnostic and relapse samples, further validating the role of STAT5B in T-cell leukemogenesis. Two separate NOTCH1 mutations were seen in minor subclones at diagnosis. Interestingly, these mutations were not seen in the relapse samples, however relapse 2 acquired a FBXW7 mutation which could render the leukemic cells renewed aberrant NOTCH1 activity. The vast majority of identified SNVs (51/66, 77%) were selectively seen in the relapsed samples. Notably, some relapse-specific mutations were detected in genes responsible for drug resistance; ABCA2 and NT5C2.
Conclusion
To elucidate genes involved in relapsed T-ALL could hopefully result in new targeted treatments.
Session topic: E-poster
Abstract: PB1593
Type: Publication Only
Background
Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood responsible for a quarter of all pediatric cancers. T-cell ALL (T-ALL) makes up 10-15% of childhood ALL. Close to 80% of children diagnosed with T-ALL survive the disease if treated according to standard protocols. However, one in five T-ALL patients relapse and for this group the outcome is very dismal, less than half of the patients are cured.
Aims
We undertook exome sequencing of matched diagnostic, remission and two relapse (relapse 1 and 2) DNA samples from a pediatric T-ALL patient.
Methods
Agilent SureSelect exome capture was used and each capture library was sequenced on the HiSeq2000 platform. >98% of the targets were sequenced with at least 20x coverage.
Results
In total, 66 somatic single nucleotide variants (SNVs) were detected in the three samples. Almost half of the SNVs detected at diagnosis were also seen at relapse 1 and/or 2 (7/15, 47%). This result hence indicates that the relapse evolves from a clone present at diagnosis. STAT5B mutations, including N642H, were recently implicated as a putative drivers of T-ALL. We identified the N642H mutations in a homozygous state in both diagnostic and relapse samples, further validating the role of STAT5B in T-cell leukemogenesis. Two separate NOTCH1 mutations were seen in minor subclones at diagnosis. Interestingly, these mutations were not seen in the relapse samples, however relapse 2 acquired a FBXW7 mutation which could render the leukemic cells renewed aberrant NOTCH1 activity. The vast majority of identified SNVs (51/66, 77%) were selectively seen in the relapsed samples. Notably, some relapse-specific mutations were detected in genes responsible for drug resistance; ABCA2 and NT5C2.
Conclusion
To elucidate genes involved in relapsed T-ALL could hopefully result in new targeted treatments.
Session topic: E-poster
Type: Publication Only
Background
Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood responsible for a quarter of all pediatric cancers. T-cell ALL (T-ALL) makes up 10-15% of childhood ALL. Close to 80% of children diagnosed with T-ALL survive the disease if treated according to standard protocols. However, one in five T-ALL patients relapse and for this group the outcome is very dismal, less than half of the patients are cured.
Aims
We undertook exome sequencing of matched diagnostic, remission and two relapse (relapse 1 and 2) DNA samples from a pediatric T-ALL patient.
Methods
Agilent SureSelect exome capture was used and each capture library was sequenced on the HiSeq2000 platform. >98% of the targets were sequenced with at least 20x coverage.
Results
In total, 66 somatic single nucleotide variants (SNVs) were detected in the three samples. Almost half of the SNVs detected at diagnosis were also seen at relapse 1 and/or 2 (7/15, 47%). This result hence indicates that the relapse evolves from a clone present at diagnosis. STAT5B mutations, including N642H, were recently implicated as a putative drivers of T-ALL. We identified the N642H mutations in a homozygous state in both diagnostic and relapse samples, further validating the role of STAT5B in T-cell leukemogenesis. Two separate NOTCH1 mutations were seen in minor subclones at diagnosis. Interestingly, these mutations were not seen in the relapse samples, however relapse 2 acquired a FBXW7 mutation which could render the leukemic cells renewed aberrant NOTCH1 activity. The vast majority of identified SNVs (51/66, 77%) were selectively seen in the relapsed samples. Notably, some relapse-specific mutations were detected in genes responsible for drug resistance; ABCA2 and NT5C2.
Conclusion
To elucidate genes involved in relapsed T-ALL could hopefully result in new targeted treatments.
Session topic: E-poster
{{ help_message }}
{{filter}}