Contributions
Abstract: S496
Type: Oral Presentation
Presentation during EHA22: On Saturday, June 24, 2017 from 16:00 - 16:15
Location: Room N104
Background
Hematologic malignancies have rarely been targets for genetic evaluation, even in familial cases. Over the past decade, more than 12 genes have been identified to cause inherited predispositions to hematologic malignancies. Genetic counseling, testing, and surveillance protocols for these families are not well-established. Additionally, many families with high incidence of blood cancers do not have described syndromes suggesting additional genes remain to be identified.
Aims
To identify individuals with inherited susceptibilities to hematologic malignancies, the Hereditary Hematologic Malignancy Clinic (HHMC) was established in April 2014 at The University of Texas M. D. Anderson Cancer Center. The clinic provides genetic counseling, clinical and research testing for patients with hematologic malignancies suspected to have inherited predisposition syndromes.
Methods
Individuals were referred to the HHMC for several indications: (1) bone marrow failure/aplastic anemia/hypocellular MDS, (2) personal history of hematologic malignancy with ≥1 first-degree relative or ≥2 second-degree relatives with hematologic malignancy, (3) personal history of multiple primary cancers, (4) germline evaluation of presumed somatic mutations identified on next-generation leukemia prognostication panels, (5) management and/or surveillance of a previously-identified genetic syndrome, or (6) solid tumor hereditary syndrome evaluation in patients with active hematologic malignancy. Over the past 3 years, 152 probands were evaluated (n=152). Skin biopsies were performed to obtain germline DNA, and next-generation sequencing approaches on both a clinical and research basis were utilized.
Results
Clinical genetic testing was performed in 97/152 individuals (64%). Research testing was performed in 46/152 (30%), particularly in patients negative for known susceptibility genes or without features suggestive of a clinical syndrome. Nine (6%) individuals did not undergo genetic testing. Clinical testing identified 23/97 (24%) individuals with a germline susceptibility to hematologic malignancy. Seven probands (7%) were identified to have RUNX1 mutations associated with familial platelet disorder with myeloid malignancy (FPD-AML). Six (6%) were identified to have the telomere disorder dyskeratosis congenita; only one of them met clinical diagnostic criteria with the 'classic triad' of symptoms. Three (3%) patients were identified to have Li-Fraumeni syndrome due to constitutional TP53 mutations. Two adults (2%) were diagnosed with Diamond-Blackfan anemia; both of these individuals developed adult-onset myelodysplastic syndrome after a long latency period and prior spontaneous remission of their childhood anemia. Two young adults (2%) with Fanconi anemia were diagnosed, and one patient each with DDX41 mutation and CBL (Noonan-like syndrome with JMML) were identified. Counseling, testing, and surveillance of identified mutation carriers in many affected families is ongoing.
Conclusion
Individuals with hereditary susceptibilities to hematologic malignancies are not as rare as previously thought. Clinical evaluation of these patients through genetic counseling and testing is high yield for identified at-risk families. Research-based sequencing for novel mutations is indicated and ongoing.
Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical
Keyword(s): familial, Dyskeratosis congenita, Acute Myeloid Leukemia, Fanconi anemia
Abstract: S496
Type: Oral Presentation
Presentation during EHA22: On Saturday, June 24, 2017 from 16:00 - 16:15
Location: Room N104
Background
Hematologic malignancies have rarely been targets for genetic evaluation, even in familial cases. Over the past decade, more than 12 genes have been identified to cause inherited predispositions to hematologic malignancies. Genetic counseling, testing, and surveillance protocols for these families are not well-established. Additionally, many families with high incidence of blood cancers do not have described syndromes suggesting additional genes remain to be identified.
Aims
To identify individuals with inherited susceptibilities to hematologic malignancies, the Hereditary Hematologic Malignancy Clinic (HHMC) was established in April 2014 at The University of Texas M. D. Anderson Cancer Center. The clinic provides genetic counseling, clinical and research testing for patients with hematologic malignancies suspected to have inherited predisposition syndromes.
Methods
Individuals were referred to the HHMC for several indications: (1) bone marrow failure/aplastic anemia/hypocellular MDS, (2) personal history of hematologic malignancy with ≥1 first-degree relative or ≥2 second-degree relatives with hematologic malignancy, (3) personal history of multiple primary cancers, (4) germline evaluation of presumed somatic mutations identified on next-generation leukemia prognostication panels, (5) management and/or surveillance of a previously-identified genetic syndrome, or (6) solid tumor hereditary syndrome evaluation in patients with active hematologic malignancy. Over the past 3 years, 152 probands were evaluated (n=152). Skin biopsies were performed to obtain germline DNA, and next-generation sequencing approaches on both a clinical and research basis were utilized.
Results
Clinical genetic testing was performed in 97/152 individuals (64%). Research testing was performed in 46/152 (30%), particularly in patients negative for known susceptibility genes or without features suggestive of a clinical syndrome. Nine (6%) individuals did not undergo genetic testing. Clinical testing identified 23/97 (24%) individuals with a germline susceptibility to hematologic malignancy. Seven probands (7%) were identified to have RUNX1 mutations associated with familial platelet disorder with myeloid malignancy (FPD-AML). Six (6%) were identified to have the telomere disorder dyskeratosis congenita; only one of them met clinical diagnostic criteria with the 'classic triad' of symptoms. Three (3%) patients were identified to have Li-Fraumeni syndrome due to constitutional TP53 mutations. Two adults (2%) were diagnosed with Diamond-Blackfan anemia; both of these individuals developed adult-onset myelodysplastic syndrome after a long latency period and prior spontaneous remission of their childhood anemia. Two young adults (2%) with Fanconi anemia were diagnosed, and one patient each with DDX41 mutation and CBL (Noonan-like syndrome with JMML) were identified. Counseling, testing, and surveillance of identified mutation carriers in many affected families is ongoing.
Conclusion
Individuals with hereditary susceptibilities to hematologic malignancies are not as rare as previously thought. Clinical evaluation of these patients through genetic counseling and testing is high yield for identified at-risk families. Research-based sequencing for novel mutations is indicated and ongoing.
Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical
Keyword(s): familial, Dyskeratosis congenita, Acute Myeloid Leukemia, Fanconi anemia