Nature Research · Web viewA right 3.4 cm renal mass was diagnosed as oncocytoma, whereas one left...
Transcript of Nature Research · Web viewA right 3.4 cm renal mass was diagnosed as oncocytoma, whereas one left...
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Supplementary Material:
Supplementary Figure S1: H&E staining and mtDNA analysis of clear cell RCC and oncocytoma from a
single patient.
Supplementary Figure S2: H&E staining and representative electropherogram of biopsy and corresponding
tumor samples.
Supplementary Table S1: Clinical information on BMF oncocytoma patients.
Supplementary Table S2: Histology and mtDNA analysis of chromophobe RCC.
Supplementary Table S3: mtDNA analysis in non-oncocytic and non-chromophobe renal tumors.
Supplementary Table S4: Genetic analysis of FLCN and mtDNA in BHD tumors.
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Supplementary Figure S1:
H&E staining and mtDNA analysis of clear cell RCC (ccRCC) and oncocytoma from a single patient
(BMF6). A and B, H&E staining of ccRCC and oncocytoma, respectively (100x magnification); C and D,
electropherogram showing mutations m.10952insC and m.G12923A in DNA extracted from oncocytoma,
which were absent from ccRCC and blood DNA.
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Supplementary Figure S2:
H&E staining and representative electropherogram of biopsy and corresponding tumor samples (BMF8).
H&E staining shows histology of biopsy sample (100x magnification) (A) and corresponding tumor sample
after surgery (200x magnification) (B). C: Gel electrophoresis of PCR reactions showing amplification of
DNA extracted from biopsy samples. D: Sequencing electropherogram showing detection of heteroplasmic
mutation m.G4244A in tumor, biopsy, and blood DNA.
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Patient Family history
Sex Clinical history Nonneoplastic kidney parenchyma
BMF1 None M Patient underwent a left partial nephrectomy at NIH at age 67, where 5 oncocytomas were removed, the largest being 2.8 cm. At age 69, biopsies were taken at NIH of 2 right renal masses, and both were diagnosed as oncocytoma. As of age 75, imaging shows 2 right renal masses and 1 left renal mass.
Histology was not available;Genetic analysis showed no mtDNA mutation
BMF2 None F Patient underwent a right partial nephrectomy at NIH at age 54, where 5 tumors were removed, the largest being 6 cm; all were diagnosed as tumors consistent with oncocytoma. At age 55, the patient had a left partial nephrectomy at NIH to remove 6 masses, all of which were oncocytoma. As of age 60, imaging shows 4 masses in her right kidney and at least 9 masses in her left kidney.
Oncocytosis
BMF3 None F Patient underwent a right partial nephrectomy at NIH at age 48 for 4 masses, the largest being 3 cm, which were diagnosed as oncocytic tumors consistent with oncocytomas. As of age 51, imaging shows 6 solid lesions in her left kidney and none remaining in her right kidney.
not available
BMF4 None M Patient underwent a left radical nephrectomy at an outside hospital at age 62. The outside pathology report described two oncocytomas (10 cm and 0.6 cm) and a small (0.3 cm) separate area of oncocytosis; our pathologist at NIH concurred. At age 63, he had a right partial nephrectomy at NIH to remove 10 tumors, the largest of which was 3.5 cm, 8 of which were called oncocytoma and 2 were called oncocytic tumors. At age 70, imaging shows 2 solid lesions in his right kidney.
Oncocytosis
BMF5 None F Patient underwent a right partial nephrectomy at NIH at age 71, where 2 masses (4.5 cm and 2.5 cm) were removed, both of which were oncocytoma. Three years later, at age 74, she had a biopsy at NIH of a left renal mass that was diagnosed as an oncocytoma.
not available
BMF6 None M Patient underwent first a right and then a left partial nephrectomy at NIH at age 66. A right 3.4 cm renal mass was diagnosed as oncocytoma, whereas one left mass was a 3.5 cm clear cell renal cell carcinoma and the other 4.0 cm left mass was a cyst and oncocytoma. As of 2 years later, at age 68, imaging shows one renal mass in the left kidney and one in the right.
not available
BMF7 None F Patient underwent a left partial nephrectomy at NIH at age 69, for a 2.5 cm oncocytoma and a 0.7 cm angiomyolipoma. Imaging information has not been available for the last 8 years.
not available
Supplementary Table S1:
Clinical information on BMF oncocytoma patients.
For every BMF oncocytoma patient, clinical history and pathology information about each tumor is given.
Availability and histology of nonneoplastic kidney parenchyma is also listed.
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Supplementary Table S2:
Histology and mtDNA analysis of chromophobe RCC.
Histologic subtype and mtDNA nucleotide changes are reported, where identified, in a total of 12
chromophobe RCC samples from 11 different patients plus one patient with multiple chromophobe RCCs.
Mutation load is given for each mutation: “hom” indicates homoplasmic and “het” heteroplasmic mutations.
Pathogenic prediction of missense mutations are indicated as PSIC score, given by PolyPhen-2. Site
variability scores are listed for each nucleotide change, as reported by the Human mitochondrial Database
(hmtdb: www.hmtdb.uniba.it, (Rubino et al. 2012)) for normal and patient samples, to identify previously
reported nucleotide changes. Column entitled “mitomap.org” reports description of nucleotide changes as
reported by mitomap.org.
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Supplementary Table S3:
mtDNA sequence analysis in non-oncocytic and non-chromophobe renal tumors.
For each sample, somatic nucleotide changes and resulting amino acid change, affected gene, homoplasmy
(hom) or heteroplasmy (het) status and mutation load for heteroplasmic samples, and PSIC score from
prediction of pathogenic potential of missense mutations with PolyPhen-2 are listed. fs indicates frameshift
mutations. Hmtdb site variability scores for normal and patient samples are listed to identify previously
reported nucleotide changes (Rubino et al. 2012).
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Supplementary Table S4:
Genetic analysis of FLCN and mtDNA in BHD tumors.
For BHD tumors of different histologies germline and somatic FLCN status is shown along with mtDNA
sequence data. “LOH” indicates somatic loss of heterozygosity at the FLCN locus. Homoplasmic (hom) or
heteroplasmic (het) status of mtDNA mutations is specified for each mutation together with the affected
genes and information on whether the nucleotide change has been previously reported (hmtdb site variability
score in normal and patient samples, (Rubino et al. 2012)). PSIC score of in silico prediction of pathogenic
potential with PolyPhen-2 is shown. Samples in which no somatic FLCN or mtDNA mutations were detected
are indicated as “ND”.
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a Mutation position is determined from the first nucleotide of the folliculin transcript, GenBank accession
number AF517523
b Mutation m.297_348del50 is described in:
Bi R, Zhang AM, Zhang W, et al. The acquisition of an inheritable 50-bp deletion in the human mtDNA control region does not affect the mtDNA copy number in peripheral blood cells. Hum Mutat. 2010; 31(5):538-43