Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations

Jennifer A. Oberg; Julia L. Glade Bender; Maria Luisa Sulis; Danielle Pendrick; Anthony N. Sireci; Susan J. Hsiao; Andrew T. Turk; Filemon S. Dela Cruz; Hanina Hibshoosh; Helen Remotti; Rebecca J. Zylber; Jiuhong Pang; Daniel Diolaiti; Carrie Koval; Stuart J. Andrews; James H. Garvin; Darrell J. Yamashiro; Wendy K. Chung; Stephen G. Emerson; Peter L. Nagy; Mahesh M. Mansukhani; Andrew L. Kung

doi:10.1186/s13073-016-0389-6

Table 3 Clinical utility beyond targetable somatic mutations

From: Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations

PIP ID	Diagnosis	Alteration	Mutation (change)	Clinical utility	Implication
Sequence mutations
15-63375	AML changed to JMML	PTPN11; SETB1	c.181G > T (p.D61Y); c.2602G > A (p.D868N)	Diagnostic [31, 46]	JMML
13-72282^a	T-ALL	STAT5B	c.2110A > C (p.I704L)	Diagnostic [30, 47]	Gamma-delta T-cell lymphoma
15-26188	ALL	NT5C2	c.1219G > T (p.D407Y)	Pharmacogenomic [32, 33]	Affects therapy
13-45348	AML	IDH1	c.394C > T (p.R132C)	Diagnostic [48, 49]	Maffucci syndrome
14-53198	AML	CEBPA	c.939_940insAAG (p.K313_V314insK); c.326_327insC (p.P109fs)	Prognostic [50]	Improved prognosis
15-10838	Glioma	H3F3A	c.83A > T (p.K28M)	Prognostic [51]	Poor prognosis
14-37237	Glioblastoma multiforme	H3F3A	c.83A > T (p.K28M)	Prognostic [52, 53]	GBM subgroup, K27
14-35585	Renal cell carcinoma	VHL	c.497 T > G (p.V166G)	Diagnostic [54]	Von Hippel Lindau
14-47205	Nephroblastomatosis	PIK3CA	c.1035 T > A (p.N345K)	Diagnostic [55]	Nephroblastomatosis
14-78154^a	Medulloblastoma	KDM6A	c.2989_2990dupAT (p.M997fs)	Prognostic [56]	Risk stratification, group 4
14-75899	Neuroblastoma	ATRX	c.5239delA (p.T1747fs)	Prognostic [57]	Poor prognosis
14-10141	Pleuropulmonaryblastoma	DICER1	c.5438A > G (p.E1813G)	Health Maintenance [58]	DICER syndrome
Transcriptome analysis and CNV
14-24794	AML	CBFB-MYH11	Fusion	Prognostic [59]	Low-risk stratification
15-64793	B-ALL	FOXP1-ABL1	Fusion	Prognostic [60]	High-risk stratification
15-84578	AMKL	CBFA2T3-GLIS2	Fusion	Diagnostic [61]; Prognostic [35]	AMKL; Poor prognosis
14-85546	CML	BCR-ABL1	Fusion	Diagnostic [59]	CML
13-72282^a	T-ALL	Isochromosome 7q	Copy number change	Diagnostic [39]	Gamma-delta T-cell lymphoma
15-46387	Rhabdomyosarcoma	PAX7-FOXO1	Fusion	Diagnostic [62, 63]; Prognostic [64]	Rhabdomyosarcoma; High-risk group
13-81192	Alveolar soft part sarcoma	ASPSCR1-TFE3	Fusion	Diagnostic [65]	Alveolar soft part sarcoma
13-65217	Ewing sarcoma	EWSR1-FLI1	Fusion	Diagnostic [66]	Ewing sarcoma
15-47087	Ewing sarcoma	EWSR1-FLI1; Low expression of PAX8, FHIT, CASP10, CHD2, with high expression of CHD11, FUS, and MTA1	Fusion; Expression pattern	Diagnostic [66]; Prognostic [36]	Ewing sarcoma; Poor prognosis
13-21968	Undifferentiated sarcoma	EML4-NTRK3	Fusion	Diagnostic [34]	Infantile fibrosarcoma
16-88073	Ependymoma	C11orf95-RELA; Alternating gains and losses on chr 11 and 22, consistent with a “chromothripsis-like” pattern	Fusion; Copy number change	Prognostic [67]; Diagnostic [68]	Poor prognosis; RELA-type supratentorial ependymoma
14-27243	Neuroblastoma	MYCN amplified, deletion at 1p and 11q, gain 17q; MYCN over expressed	Copy number change; Overexpression	Prognostic [69, 70]	Risk-based therapy
14-42817	Neuroblastoma	MYCN non-amplified, no LOH at 1p11q; MYCN not over expressed	Copy number change; No overexpression	Prognostic [69, 70]	Risk-based therapy
15-39486	Neuroblastoma	MYCN non-amplified, no LOH at 1p11q; MYCN not over expressed	Copy number change; No overexpression	Prognostic [69, 70]	Risk-based therapy
14-44070	Neuroblastoma	MYCN amplified, loss of 1p, gain of 1q and 17q; MYCN over expressed	Copy number change; Overexpression	Prognostic [69, 70]	Risk-based therapy
15-88980	Hepatoblastoma	Amplification of 11q13.2 including CCND1; Over expression of CCND1	Copy number change; Overexpression	Prognostic [71]	Good prognosis
15-49177	Medulloblastoma	IMPG2, GABRA5, LAPTM4B, MAB21L2, NPR3, MFAP4, NRL, ZFPM2, TSHZ3, IGF2BP3, GALNT14, GPR98; Loss of 10q22.2-10qter involving PTEN and SUFU, loss of 17p, gain of 17q	Overexpression; Copy number change	Prognostic [72]	Risk stratification, subgroup 3/4
15-70532	Ependymoma	Gain of 1q, loss of 6q	Copy number change	Prognostic [73–75]	Poor prognosis
14-78154^a	Medulloblastoma	KCNA1, RBM24, KLHL13, EN2, SNCAIP, PDE1C, GRM8, KCNIP4, EXPH5, UNC5D, NID2, ST18, GPR12, SH3GL3; i17q	Overexpression; Copy number change	Prognostic [72]	Risk stratification, subgroup 4
15-40141	Pleomorphic xanthoastrocytoma	Gain of chromosome 7, LOH at 9p	Copy number change	Diagnostic [76]	Pleomorphic xanthoastrocytoma
15-97336	Small round blue cell tumor	EWSR1-WT1	Fusion	Diagnostic [77]	DSRCT
15-34296	Ependymoma	TNC, CALB1, PLAG1, ALDH1L1, RELN	Overexpression	Prognostic [37]	Risk stratification, group A, poor prognosis
15-80972	ATRT	LOH at 22q11.21qter, including SMARCB1; ASCL1	Copy number change; Overexpression	Diagnostic [78]; Prognostic [79]	ATRT; Improved prognosis

^aSame patient
ALL acute lymphoblastic leukemia, AMKL acute megakaryoblastic leukemia, AML acute myeloid leukemia, ATRT atypical teratoid rhaboid tumor, CML chronic myeloid leukemia, CNV copy number variation, JMML juvenile myelomonocytic leukemia

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