Table 2. The susceptible tissue/subtissue and cancer type associated with the TSGs and POGs identified for analysis, plus the expression of these genes in susceptible vs nonsusceptible tissues.
Gene type | Gene | High-penetrance cancer | Susceptible tissue type | Kruskal–Wallis test P-value | Expression (susc. tissue) | Expression (other tissues) | Significance category | Relative expression | Susceptible subtissue | Rel. expr. in susc. subtissue | Subtissue significance category |
---|---|---|---|---|---|---|---|---|---|---|---|
Tumour suppressor genes | ATM | Leukaemia, lymphoma | Immune system | 5.06E−15 | 2.886±0.472 | −0.028±0.206 | A (2) | 7.54 | Lymph node | 11.68 | A (1) |
STK11 | gastrointestinal polyps | Gastrointestinal | 5.06E−15 | 1.814±0.173 | 0.108±0.224 | A (2) | 3.26 | Small intestine | 3.34 | A (3) | |
NF1 | Glioma, other CNS cancers | Brain and nerve | 5.06E−15 | 0.645±0.076 | −0.432±0.205 | A (1) | 2.11 | NA | |||
RB1 | Osteosarcoma | Bone | 5.06E−15 | 0.62±0.203 | −0.060±0.123 | A (2) | 1.60 | NA | |||
SMAD4 | Gastrointestinal polyps | Gastrointestinal | 1.29E−03 | 0.878±0.324 | 0.260±0.106 | A (2) | 1.53 | Small intestine | 2.21 | A (1) | |
CDKN2A | Melanoma | Skin | 2.99E−07 | 0.904±0.510 | 0.386±0.389 | B | 1.43 | Epidermis | 0.41 | E | |
MEN1 | Parathyroid adenoma | Endocrine | 5.06E−15 | −0.246±0.139 | −0.758±0.249 | B | 1.43 | Thyrocyte | 1.26 | A (7) | |
BRCA2 | Prostate | Male reproductive | 1.17E−10 | 0.106±0.190 | −0.237±0.194 | BC | 1.27 | Prostate gland | 1.01 | A (6) | |
PRKAR1A | Myxoma | Heart and muscle | 5.06E−15 | 0.655±0.099 | 0.015±0.331 | BC | 1.56 | Heart | 2.36 | A (2) | |
PHOX2B | Neuroblastoma | Brain and nerve | 2.02E−12 | −0.066±0.067 | 0.134±0.203 | BC | 0.87 | NA | |||
PTCH1 | Skin basal cell | Skin | 5.06E−15 | −0.069±0.116 | 0.136±0.156 | BC | 0.69 | Keratinocyte | 0.86 | BC | |
MLH1 | Endometrial | Female reproductive | 5.06E−15 | −0.211±0.088 | −0.387±0.190 | CD | 1.13 | Placenta basal plate | 1.19 | CD | |
BRCA1 | Ovarian | Female reproductive | 5.06E−15 | −0.779±0.070 | −0.394±0.173 | CDE | 0.77 | Ovary | 0.77 | DE | |
TP53 | Osteosarcoma | Bone | 5.06E−15 | −0.378±0.045 | −0.222±0.172 | D | 0.90 | NA | |||
MSH2 | Ovarian | Female reproductive | 5.06E−15 | −0.807±0.081 | −0.487±0.157 | DE | 0.80 | Ovary | 1.67 | A (3) | |
PRKAR1A | Testicular | Male reproductive | 5.06E−15 | −0.198±0.260 | 0.093±0.335 | EF | 0.82 | NA | |||
TSG average: | 0.368±0.254 | −0.130±0.082 | |||||||||
Proto-oncogenes | RET | Medullary thyroid | Endocrine | 1.40E−11 | 7.097±2.437 | 0.158±0.164 | A (3) | 122.77 | NA | ||
TSHR | Thyroid adenoma | Endocrine | 7.13E−03 | 6.588±4.292 | 0.868±0.399 | A (1) | 52.72 | NA | |||
MPL | Myeloproliferative disorder | Bone | 1.08E−12 | 2.594±0.598 | 0.519±0.211 | A (1) | 4.21 | NA | |||
ALK | Neuroblastoma | Brain and nerve | 5.06E−15 | 0.697±0.065 | −0.261±0.108 | A (1) | 1.94 | NA | |||
EGFR | Non-small-cell lung cancer | Epithelium | 5.06E−15 | 0.473±0.056 | 0.112±0.186 | A (5) | 1.28 | NA | |||
LMO1 | Neuroblastoma | Brain and nerve | 7.59E−07 | 0.179±0.076 | 0.106±0.140 | ABCD | 1.05 | NA | |||
KIT | Gastrointestinal stromal tumour | Gastrointestinal | 5.06E−15 | 1.053±0.255 | 1.062±0.138 | CD | 0.99 | Small intestine | 0.79 | CD | |
HRAS | Rhabdomyosarcoma | Heart and muscle | 5.06E−15 | −0.743±0.089 | −0.76±0.329 | DE | 1.01 | Skeletal muscle | 1.6 | C | |
POG average: | 2.24±1.06 | 0.225±0.209 |
Abbreviations: CNS= central nervous system; NA=not applicable; POG=proto-oncogene; Rel. expr.=relative expression; susc.=susceptible; TSG=tumour suppressor gene.
For each gene, results are shown for the Kruskal–Wallis test across the 12 broad tissue categories (P-value=significance after Bonferroni correction) and the significance categories assigned to the susceptible tissue in the subsequent Kruskal–Wallis multiple comparison test. For genes in significance category ‘A', the total number of tissues tied in that category is given in parentheses. Also shown are the log2 expression (±1 s.e.) of each gene in the susceptible tissue type, the mean for the 11 other tissues and the ratio of these expression levels. For those genes that could also be analysed at the level of subtissue, the results from the subtissue analysis are also shown.