Table 2.
Distribution of 220 Pathogenic or Likely Pathogenic Variants in 205 Patients With Advanced Cancer Consenting to Tumor-Normal Genomic Analysis
| Gene Mutated in Tumor Type | Patients With Advanced Cancer With Pathogenic Variants | Total Pathogenic Variants per Gene, No. | |
|---|---|---|---|
| Total per Gene, No. | By Tumor Type (No. of Pathogenic Variants Detected by Gene and Tumor Type) | ||
| High Penetrance | |||
| BAP1 | 3 | Mesothelioma (1), renal cell (2) | 3 |
| BRCA1 | 14 | Bladder (1), breast (2), esophagogastric (1), ovarian (2), pancreatic (6), prostate (2) | 14 |
| BRCA2 | 45 | Ampullary (1), biliary (3), breast (1), esophagogastric (1), melanoma (1), ovarian (3), pancreatic (11), prostate (24) | 45 |
| CDH1 | 2 | Esophagogastric (2) | 2 |
| CDKN2A | 3 | Pancreatic (3) | 3 |
| FH | 3 | Renal cell (3) | 3 |
| FLCN | 1 | Prostate (1) | 1 |
| MEN1 | 1 | Non–small cell lung (1) | 1 |
| MLH1 | 1 | Bladder (1) | 1 |
| MSH2 | 7 | Bladder (4), colorectal (2), prostate (1) | 7 |
| MSH6 | 4 | Bladder (2), prostate (1), renal cell (1) | 4 |
| PALB2 | 5 | Biliary (1), ovarian (1), pancreatic (1), prostate (1), renal cell (1) | 5 |
| PMS2 | 2 | Prostate (1), small-bowel (1) | 2 |
| SDHA | 2 | Breast (1), renal cell (1) | 2 |
| SDHB | 2 | Paraganglioma (1), renal cell (1) | 2 |
| VHL | 2 | Renal cell (2) | 2 |
| Moderate Penetrance | |||
| ATM | 15 | Breast (1), colorectal (1), esophagogastric (1), pancreatic (5), prostate (7) | 15 |
| BRIP1 | 4 | Breast (1), colorectal (1), prostate (2) | 4 |
| CHEK2 | 28a | Breast (9), colorectal (1), endometrial (2), pancreatic (7), prostate (8), renal cell (5) | 32 |
| MITF | 2 | Prostate (2) | 2 |
| NBN | 2 | Prostate (2) | 2 |
| RAD51D | 1 | Non–small cell lung (1) | 1 |
| Low Penetrance | |||
| APC | 19a | Biliary (1), bladder (1), breast (1), colorectal (3), ovarian (1), pancreatic (7), prostate (7), renal cell (1), small-bowel (1), unknown primary (1) | 24 |
| MUTYH | 14a | Adrenocortical (1), biliary (1), breast (1), colorectal (1), pancreatic (3), prostate (5), renal cell (3), unknown primary (1) | 16 |
| Recessive Alleles | |||
| FHb | 3a | Pancreatic (1), prostate (4) | 5 |
| RECQL4 | 5a | Breast (1), colorectal (1), endometrial (1), esophagogastric (1), prostate (1), renal cell (1) | 6 |
| Uncertain Clinical Actionability | |||
| BARD1 | 3 | Pancreatic (1), prostate (1), renal cell (1) | 3 |
| CHEK2c | 11 | Bladder (1), breast (1), endometrial (1), pancreatic (2), prostate (5), renal cell (1) | 11 |
| FAM175A | 0a | Pancreatic (1) | 1 |
| RAD50 | 1 | Pancreatic (1) | 1 |
| Total | |||
| Pathogenic variants by tumor type | 205 | Adrenocortical (1), ampullary (1), biliary (6), bladder (10), breast (19), colorectal (10), endometrial (4), esophagogastric (6), melanoma (1), mesothelioma (1), non–small cell lung (2), ovarian (7), pancreatic (49), paraganglioma (1), prostate (75), renal cell (23), small-bowel (2), unknown primary (2) | 220 |
a
For the determination of the total number of patients with advanced cancer with pathogenic variants per gene, patients with 2 pathogenic variants were classified according to the higher-penetrance variant (eAppendix 5 in Supplement 1), resulting in different values compared with the total number of pathogenic variants by gene.
b
Refers to the FH c. 1431_1433dupAAA (p. Lys477dup) mutation considered as a recessive allele.
c
Refers to the CHEK2 c.470T>C (p.Ile157Thr) mutation classified as a variant of uncertain clinical actionability.