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. 2023 Dec 15;11(6):101196.
doi: 10.1016/j.gendis.2023.101196. eCollection 2024 Nov.

Biallelic inactivation of SDHA results in comorbidity of pediatric recurrent neuroblastoma and gastric stromal tumor

Shen Yang  1 , Shixuan Zhang  2 , Wen Zhao  3 , Libing Fu  4 , Li Zhang  5 , Chan Hon Chui  6 , Ruolan Guo  7 , Yan Su  3 , Dayan Sun  8 , Huanmin Wang  1   9
Affiliations

Biallelic inactivation of SDHA results in comorbidity of pediatric recurrent neuroblastoma and gastric stromal tumor

Shen Yang et al. Genes Dis. .
No abstract available

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Figures

Figure 1
Figure 1
Biallelic inactivation of a germline truncating variant and a somatic copy number deletion in SDHA results in the comorbidity of pediatric recurrent neuroblastoma (NB) and gastrointestinal stromal tumor (GIST). (A) Pedigree chart of the proband's family. Males are depicted as squares and females as circles. Black-filled symbols represent individuals who are clinically affected. A dot in squares or circles indicates the carrier. The proband who underwent whole exome sequencing is indicated by an arrow. (B) The flow chart of the patient's clinical course of treatment. CR, complete response. (C) (1) Abdominal enhanced computed tomography (CT) at the time of initial diagnosis. (2) Whole-body positron emission tomography (PET)/CT at the time of initial diagnosis. (3) A postoperative pathological investigation of the retroperitoneal mass confirmed that NB (right adrenal gland) changed after chemotherapy. (4) The pathology of gastric mass was low-grade malignancy GIST. The arrows indicate a GIST lesion. (5) Abdominal enhanced CT at the time of tumor recurrence. (6) Whole-body PET/CT at the time of tumor recurrence. (7) The pathology of the pancreatic mass was pancreatic tail NB (poorly differentiated). (8) The pathology of gastric mass was GIST. The arrows indicate the recurrent GIST lesion. (D) The amino acid changes of the germline truncating variant on SDHA protein domains derived from the PFAM database. (E) The chromosomal region of the somatic loss-of-heterozygosity identified by saasCNV. The copy number variation regions were jointly segmented by read depth (log2ratio) and allele-specific read depth (log2mBAF). (F) Sanger sequencing chromatogram depicts the germline mutation of SDHA. (G) (1) The protein expression levels of mitochondrial complex subunits and the transcription factor of mitochondrial complex subunits of the adjacent tumor tissue and tumor tissue of recurrent GIST and NB. (2) The expression of mitochondrial fusion- and mitochondrial fission-related proteins. (3) The expression of mitochondrial quality control-related proteins. (H) (1) Immunohistochemistry (IHC) results of the SDHA expression in recurrent NB and GIST and adjacent tissues. (2) IHC results of the SDHB expression in recurrent NB and GIST. (I) (1) Mitochondrial respiratory chain complex II with acting substrates and acting structural regions. (2) The rs746165168 (Arg352Ter) mutation in SDHA and the structural region of the protein, where the grey part represents translation arrest and the purple part represents the normally translated peptide chain. (3) Flavin adenine dinucleotide (FAD) molecular structure. (4) Interaction of the SDHA protein C-chain with FAD, with yellow for hydrogen-kin, grey for translation-terminated amino acids, and purple for normal translation amino acids.
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References

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