Cancer type considerations for COSMIC signature extraction
Source:vignettes/cosmic_cancer_type_note.Rmd
cosmic_cancer_type_note.RmdThe trinuc_mutation_rates() function uses mutational
signature extraction to calculate relative trinucleotide-specific SNV
mutation rates in tumors. The “signatures_to_remove” option allows some
signatures to be excluded from this analysis, which means each tumor
will receive a weight of 0 for these signatures, indicating that none of
the tumor’s SNVs are attributable to these signatures. This page
describes the behavior of the helper function
suggest_cosmic_signature_exclusions() and the reasoning
behind it.
As reported in Alexandrov 2020,
and in COSMIC v3.1/v3.2 mutational signature releases, some signatures
are only expected to appear in certain cancer types. For more reliable
signature extraction, consider excluding implausible signatures when
running trinuc_mutation_rates().
There are also some signatures associated with various drug treatments (SBS11, SBS31, SBS32, SBS35, SBS86, SBS87, SBS90), so you if you know that your samples are treatment-naive or haven’t been exposed to the implicated drugs, some or all of these signatures can be excluded.
Note that while some COSMIC signatures are attributed to sequencing artifacts, you shouldn’t exclude these because cancereffectsizeR already handles these signatures specially.
The suggest_cosmic_signature_exclusions() function will
identify possible signature exclusions based on cancer type and
treatment status.
suggest_cosmic_signature_exclusions(cancer_type = "BRCA", treatment_naive = TRUE)
suggest_cosmic_signature_exclusions(cancer_type = "Kidney-RCC")The cancer type recommendations are based on Extended Data Figure 5
of Alexandrov 2020 and the COSMIC website (for signatures released after
the paper’s publication). The first two columns of the table below give
the labels accepted by the cancer_type argument.
Before excluding signatures, make sure your data set does not contain tumors from multiple PCAWG categories. For example, TCGA HNSC (head and neck cancer) includes oral cancers, which are listed separately here as Oral-SCC, so excluding all signatures that do not appear in Head-SCC (such as SBS29, tobacco chewing) would not be appropriate.
(You can access a text version of this table here.)
| PCAWG | Applicable TCGA | Description | SBS signatures found |
|---|---|---|---|
| ALL | (none) | acute lymphoblastic leukemia | SBS1, SBS2, SBS5, SBS7a, SBS7b, SBS7c, SBS7d, SBS10c, SBS10d, SBS13, SBS18, SBS40, SBS84, SBS85, SBS86, SBS87 |
| Biliary-AdenoCA | CHOL | biliary adenocarcinoma | SBS1, SBS2, SBS3, SBS4, SBS5, SBS9, SBS10a, SBS10b, SBS10c, SBS10d, SBS12, SBS13, SBS15, SBS16, SBS17a, SBS17b, SBS18, SBS20, SBS21, SBS22, SBS24, SBS28, SBS29, SBS32, SBS38, SBS40, SBS42, SBS44, SBS86, SBS87 |
| Bladder-TCC | BLCA | bladder transitional cell carcinoma | SBS1, SBS2, SBS3, SBS5, SBS8, SBS10a, SBS10b, SBS10c, SBS10d, SBS13, SBS18, SBS19, SBS22, SBS29, SBS40, SBS86, SBS87, SBS88, SBS92 |
| Bone-Osteosarc | (none) | sarcoma, bone | SBS1, SBS2, SBS3, SBS5, SBS8, SBS10c, SBS10d, SBS13, SBS17a, SBS17b, SBS30, SBS40, SBS86, SBS87 |
| Bone-Other | (none) | Paper vague; presumably bone cartilaginous neoplasm osteoblastoma, bone osteofibrous dysplasia, bone neoplasm epithelioid | SBS1, SBS2, SBS5, SBS8, SBS10c, SBS10d, SBS13, SBS17a, SBS17b, SBS40, SBS86, SBS87 |
| Breast | BRCA | breast adenocarcinoma, ductal carcinoma in situ, breast lobular carcinoma | SBS1, SBS2, SBS3, SBS5, SBS8, SBS9, SBS10a, SBS10b, SBS10c, SBS10d, SBS13, SBS15, SBS17a, SBS17b, SBS18, SBS19, SBS21, SBS26, SBS29, SBS30, SBS34, SBS37, SBS39, SBS40, SBS41, SBS44, SBS86, SBS87, SBS90 |
| Cervix | CESC | cervical squamous cell carcinoma and adenocarcinoma | SBS1, SBS2, SBS5, SBS6, SBS10a, SBS10b, SBS10c, SBS10d, SBS13, SBS15, SBS17a, SBS17b, SBS18, SBS26, SBS28, SBS33, SBS40, SBS44, SBS86, SBS87 |
| CNS-GBM | GBM | CNS glioblastoma | SBS1, SBS2, SBS5, SBS10a, SBS10b, SBS10c, SBS10d, SBS11, SBS13, SBS15, SBS30, SBS37, SBS40, SBS42, SBS86, SBS87 |
| CNS-LGG | LGG | CNS lower-grade glioma | SBS1, SBS5, SBS7b, SBS7c, SBS7d, SBS10c, SBS10d, SBS11, SBS19, SBS86, SBS87 |
| CNS-Medullo | (none) | CNS medulloblastoma | SBS1, SBS3, SBS5, SBS8, SBS10c, SBS10d, SBS18, SBS39, SBS40, SBS86, SBS87 |
| CNS-Oligo | (none) | CNS oligodenroglioma | SBS1, SBS5, SBS8, SBS10c, SBS10d, SBS40, SBS86, SBS87 |
| CNS-PiloAstro | (none) | CNS pilocytic astrocytoma | SBS1, SBS5, SBS10c, SBS10d, SBS19, SBS23, SBS40, SBS86, SBS87 |
| ColoRect-AdenoCA | COAD, READ | colorectal adenocarcinoma | SBS1, SBS2, SBS3, SBS5, SBS6, SBS9, SBS10a, SBS10b, SBS10c, SBS10d, SBS13, SBS15, SBS17a, SBS17b, SBS18, SBS20, SBS21, SBS26, SBS28, SBS30, SBS37, SBS40, SBS41, SBS44, SBS86, SBS87, SBS88, SBS94 |
| Eso-AdenoCA | ESCA | esophagus adenocarcinoma | SBS1, SBS2, SBS3, SBS4, SBS5, SBS6, SBS7b, SBS7c, SBS7d, SBS10c, SBS10d, SBS13, SBS16, SBS17a, SBS17b, SBS18, SBS20, SBS26, SBS28, SBS34, SBS38, SBS40, SBS44, SBS86, SBS87, SBS90 |
| Eso-SCC | ESCA | esophagus squamous cell carcinoma | SBS1, SBS2, SBS5, SBS9, SBS10b, SBS10c, SBS10d, SBS13, SBS15, SBS17a, SBS17b, SBS18, SBS22, SBS36, SBS44, SBS86, SBS87, SBS90, SBS93 |
| Ewings | (none) | Ewing’s sarcoma | SBS1, SBS2, SBS5, SBS7a, SBS7b, SBS7c, SBS7d, SBS10c, SBS10d, SBS13, SBS18, SBS35, SBS40, SBS86, SBS87 |
| Eye-Melanoma | UVM | uveal melanoma | SBS1, SBS5, SBS10c, SBS10d, SBS40, SBS86, SBS87 |
| Head-SCC | HNSC | head-and-neck squamous cell carcinoma (note HNSC also includes some Oral-SCC) | SBS1, SBS2, SBS3, SBS4, SBS5, SBS7a, SBS7b, SBS7c, SBS7d, SBS10a, SBS10b, SBS10c, SBS10d, SBS13, SBS15, SBS16, SBS17a, SBS17b, SBS18, SBS21, SBS30, SBS32, SBS33, SBS36, SBS38, SBS39, SBS40, SBS44, SBS86, SBS87, SBS88 |
| Kidney-ChRCC | (none) | kidney chromophobe renal cell carcinoma | SBS1, SBS2, SBS5, SBS10c, SBS10d, SBS13, SBS17a, SBS17b, SBS29, SBS40, SBS86, SBS87 |
| Kidney-Papillary | KIRP | papillary renal cell carcinoma | SBS1, SBS2, SBS5, SBS10c, SBS10d, SBS13, SBS86, SBS87 |
| Kidney-RCC | KIRC | kidney renal cell carcinoma | SBS1, SBS2, SBS4, SBS5, SBS10c, SBS10d, SBS12, SBS13, SBS14, SBS22, SBS26, SBS29, SBS40, SBS41, SBS86, SBS87 |
| Liver-HCC | LIHC | liver hepatocellular carcinoma | SBS1, SBS3, SBS4, SBS5, SBS6, SBS9, SBS10c, SBS10d, SBS12, SBS14, SBS16, SBS17a, SBS17b, SBS18, SBS19, SBS22, SBS23, SBS24, SBS26, SBS28, SBS29, SBS30, SBS31, SBS35, SBS37, SBS40, SBS86, SBS87 |
| Lung-AdenoCA | LUAD | lung adenocarcinoma | SBS1, SBS2, SBS3, SBS4, SBS5, SBS6, SBS9, SBS10c, SBS10d, SBS13, SBS15, SBS17a, SBS17b, SBS18, SBS28, SBS29, SBS40, SBS86, SBS87 |
| Lung-SCC | LUSC | lung squamous cell carcinoma | SBS1, SBS2, SBS3, SBS4, SBS5, SBS7a, SBS7b, SBS7c, SBS8, SBS10c, SBS10d, SBS13, SBS15, SBS18, SBS29, SBS30, SBS40, SBS44, SBS86, SBS87 |
| Lymph-BNHL | (none) | lymphoid mature B-cell lymphoma | SBS1, SBS2, SBS3, SBS5, SBS6, SBS9, SBS10c, SBS10d, SBS13, SBS17a, SBS17b, SBS34, SBS36, SBS37, SBS40, SBS42, SBS84, SBS85, SBS86, SBS87 |
| Lymph-CLL | (none) | lymphoid chronic lymphocytic leukemia | SBS1, SBS5, SBS9, SBS10c, SBS10d, SBS18, SBS40, SBS84, SBS85, SBS86, SBS87 |
| Myeloid-AML | LAML | acute myeloid leukemia | SBS1, SBS5, SBS10c, SBS10d, SBS18, SBS19, SBS31, SBS40, SBS86, SBS87 |
| Myeloid-MDS/MPN | (none) | myelodysplastic syndrome and myeloproliferative neoplasm | SBS1, SBS2, SBS5, SBS10c, SBS10d, SBS19, SBS23, SBS32, SBS86, SBS87 |
| Oral-SCC | (none) | oral squamous cell carcinoma (note some TCGA HNSC are oral) | SBS1, SBS2, SBS5, SBS7a, SBS7b, SBS7c, SBS7d, SBS10b, SBS10c, SBS10d, SBS13, SBS20, SBS29, SBS86, SBS87, SBS88 |
| Ovary-AdenoCA | OV | ovary adenocarcinoma | SBS1, SBS2, SBS3, SBS5, SBS7b, SBS7c, SBS7d, SBS8, SBS10c, SBS10d, SBS13, SBS18, SBS26, SBS35, SBS38, SBS39, SBS40, SBS41, SBS86, SBS87 |
| Panc-AdenoCA | PAAD | pancreatic adenocarcinoma | SBS1, SBS2, SBS3, SBS5, SBS6, SBS8, SBS10a, SBS10b, SBS10c, SBS10d, SBS13, SBS14, SBS15, SBS17a, SBS17b, SBS18, SBS20, SBS26, SBS28, SBS30, SBS31, SBS34, SBS37, SBS40, SBS44, SBS86, SBS87 |
| Panc-Endocrine | (none) | pancreatic neuroendocrine tumor | SBS1, SBS2, SBS3, SBS5, SBS6, SBS8, SBS9, SBS10c, SBS10d, SBS11, SBS13, SBS17a, SBS17b, SBS26, SBS30, SBS36, SBS39, SBS40, SBS86, SBS87 |
| Prost-AdenoCA | PRAD | prostate adenocarcinoma | SBS1, SBS2, SBS3, SBS5, SBS6, SBS8, SBS10c, SBS10d, SBS12, SBS13, SBS18, SBS33, SBS37, SBS39, SBS40, SBS41, SBS86, SBS87 |
| Sarcoma | SARC | sarcoma | SBS1, SBS5, SBS7a, SBS7b, SBS7c, SBS7d, SBS10c, SBS10d, SBS18, SBS40, SBS86, SBS87 |
| Sarcoma-bone | (none) | paper unclear; perhaps osteosarcoma and other sarcomas combined? | SBS1, SBS2, SBS5, SBS7a, SBS7b, SBS7c, SBS7d, SBS10c, SBS10d, SBS13, SBS18, SBS35, SBS40, SBS86, SBS87 |
| Skin-BCC | (none) | skin basal cell carcinoma | SBS1, SBS2, SBS5, SBS7a, SBS7b, SBS7c, SBS7d, SBS10c, SBS10d, SBS86, SBS87 |
| Skin-Melanoma | SKCM | skin melanoma | SBS1, SBS2, SBS3, SBS5, SBS7a, SBS7b, SBS7c, SBS7d, SBS9, SBS10c, SBS10d, SBS11, SBS13, SBS14, SBS17a, SBS17b, SBS31, SBS36, SBS38, SBS40, SBS86, SBS87 |
| Skin-SCC | (none) | skin squamous cell carcinoma | SBS1, SBS2, SBS5, SBS6, SBS7a, SBS7b, SBS7c, SBS7d, SBS10c, SBS10d, SBS13, SBS40, SBS86, SBS87 |
| SoftTissue-Leiomyo | (none) | leiomyosarcoma soft tissue | SBS1, SBS2, SBS5, SBS10c, SBS10d, SBS13, SBS17a, SBS17b, SBS30, SBS40, SBS86, SBS87 |
| SoftTissue-Liposarc | (none) | liposarcoma soft tissue | SBS1, SBS2, SBS3, SBS5, SBS10c, SBS10d, SBS13, SBS37, SBS40, SBS86, SBS87 |
| Stomach-AdenoCA | STAD | stomach adenocarcinoma | SBS1, SBS2, SBS3, SBS5, SBS6, SBS8, SBS10a, SBS10b, SBS10c, SBS10d, SBS13, SBS14, SBS15, SBS17a, SBS17b, SBS18, SBS20, SBS21, SBS26, SBS28, SBS34, SBS40, SBS41, SBS44, SBS86, SBS87, SBS93 |
| Thy-AdenoCA | THCA | thyroid low-grade adenocarcinoma | SBS1, SBS2, SBS5, SBS6, SBS10c, SBS10d, SBS13, SBS29, SBS40, SBS86, SBS87 |
| Uterus-AdenoCA | UCEC | uterus adenocarcinoma | SBS1, SBS2, SBS3, SBS5, SBS6, SBS7a, SBS7b, SBS7d, SBS10a, SBS10b, SBS10c, SBS10d, SBS13, SBS14, SBS15, SBS20, SBS21, SBS26, SBS28, SBS30, SBS40, SBS44, SBS86, SBS87 |