Overview of the immunohistochemical and sequencing results from 35 non-paraganglionic tumors
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1 Supplemental Figure 1. Overview of the immunohistochemical and sequencing results from 35 non-paraganglionic tumors arising in 26 SDH mutation carriers. Abbreviations Supplemental Figure 1: SDH: succinate dehydrogenase; PCC: pheochromocytoma; PGL: paraganglioma; IHC: immunohistochemistry; pos: positive; neg: negative; het: heterogenous, : loss of heterozygosity; ROH: retention of heterozygosity; WT: wild-type.
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3 Supplemental Table 1: clinico-pathological and molecular genetic characteristics of non-paraganglionic tumors arising in SDH mutation carriers Case no Age a /sex Germline SDH mutation 1 56/M SDHD 2 61/M b SDHD 3 38/F c SDHD p.pro81leu c.242c>t 4 55/F SDHD 5 42/M SDHB 6 45/M d SDHB 7 49/F SDHA p.arg31* c.91c>t 8 56/F b SDHD Tumors observed (age at detection) pnet (56) oligodendroglioma (57) GCT (L+R) (56) GVT (R) (56) macro-prolactinoma (61) PCC (R) (61) GJTT (R) (60) GCT (L) (60) GVT (L+R) (60) breast cancer (38) GCT (L) (38) gastric GIST (55) GCT (L+R) (50) GVT (L) (50) abdominal ganglioneuroma (42) GVT (R) (42) RCC L foci 1 (45) RCC L foci 2 (45) RCC R (45) gastric GIST (45) macroprolactinoma (49) GCT (R) (26) GCT (L) (49) Meningiomas (49) pituitary adenoma, GH producing (56) GCT (L+R) (56) SDHB IHC SDHA IHC Second inactivation hit Status at last follow-up (age) # Died (64) AWED (69) Heterogen ous^ ROH Died due to breast cancer (41) # AWED (64) ROH AWED (50) AWED (47) p.d38v AWD (meningiomas) (65) ROH Died (71)
4 9 70/M SDHD p.asp113fs c.337_340del GACT 10 48/F e SDHD 11 40/F SDHD 12 57/M SDHD p.leu139pro c.416t>c 13 57/F SDHD 14 57/M SDHD 15 68/M SDHD 16 37/M SDHD c.274g>t 17 37/F SDHD GJT (R) (56) GVT (R) (56) bladder cancer (70) Died (73) basal cell carcinoma (71) GCT (L+R) (NA) GJT (R) (NA) endometrial cancer (48) AWED (59) GCT (L+R) (45) GJT breast cancer (40) AWED (55) GJT (R) (40) GVT (L) (51) Hodgkin lymphoma (18) melanoma (57) AWED (71) breastcancer GCT (L+R) (65) melanoma shoulder (57) PCC (R) (55) GCT (L+R) (NA) prostate cancer (68) GJTT (L) (57) abdominal PGL (65) testicular cancer (37) prostate cancer (53) GCT (L+R) (47) GJT (L) (47) GVT (L+R) (48) papillary thyroid carcinoma (37) GCT (L+R) (37) GVT (R) (37) AWED (71) AWED (61) Died due to prostate cancer (71) AWED (62) AWED (63)
5 18 56/M SDHD 19 35/F SDHD p.leu139pro c.416t>c 20 64/F SDHD 21 65/M SDHD p.leu139pro c.416t>c 22 50/F SDHD 23 46/F SDHB 24 33/F SDHB 25 26/F SDHB 26 48/M SDHB p.thr110pro unclassified variant c.328a>c bladder cancer (56) GCT (L) (38) GJTT (L) (38) GVT (R) (38) breast cancer (R) (35) breast cancer (L) (47) GCT (L) (41) GVT (R) (42) meningioma (64) mediastinal PGL (67) prostate cancer (65) gastric GIST (41) GCT (L+R) (57) GVT (L+R) (57) PCC (L) (62) meningeoma (50) breast cancer (45) basal cell carcinoma (46) breast cancer (33) PGL NA melanoma (26) sebaceous gland carcinoma of the eyelid (48) AWD (63) AWED (49) Died due to malignant PGL (74) NA NA AWED (70) AWED (55) AWED (50) Died due to breast cancer (49) AWED (49) AWED (67) a: age at diagnosis of non-pcc/pgl tumor b: patient previously described by Papathomas et al. (12)
6 c: also BRCA1 positive d: patient previously described by Gill A et al (16) e: also heterozygosity for mutation 467C>G, S156X (MSH-6) loss of wild-type allele or somatic mutation. ^ Heterogenous defined as granular cytoplasmic staining combined with a cytoplasmic blush lacking definite granularity or completely absent staining in the presence of an internal positive control throughout the same slide Abbreviations: M: male; F: female; IHC: immunohistochemistry; pnet:pancreatic neuroendocrine tumor; GCT: glomus caroticum tumor; GVT glomus vagale tumor; GJT: glomus jugulare tumor; GJTT: glomus jugulotympanicum tumor; GTT: glomus tympanicum tumor; PGL: paraganglioma; PCC: pheochromocytoma; RCC: renal cell carcinoma; GIST: gastrointestinal stromal tumor; L: left; R: right; GH: growth hormone; AWD: alive with (non-paraganglionic) disease; AWED: alive without evidence of disease other than head and neck PGL; NA: not available; ROH: retention of heterozygosity; : loss of heterozygosity #: only one marker (centromeric or telomeric) was informative in each tumor as indicative of. Sanger (direct) sequencing showed loss of the wildtype allele.
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