2017 ASCO Annual Meeting!
Session: Cancer Prevention, Hereditary Genetics, and Epidemiology
Type: Oral Abstract Session
Time: Monday June 5, 8:00 AM to 11:00 AM
Prevalence of homologous recombination deficiency among all tumor types.
Cancer Prevention, Hereditary Genetics, and Epidemiology
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr 1502)
Author(s): Arielle Lutterman Heeke, Tabari Baker, Filipa Lynce, Michael J. Pishvaian, Claudine Isaacs; Georgetown Lombardi Comprehensive Cancer Center, Washington, DC; Caris Life Sciences, Phoenix, AZ
Background: Triple negative breast and ovarian cancer are known to have a high frequency of homologous recombination deficiencies (HRDef). The prevalence of HRDef among all tumors is unknown. Methods: Molecular profiles of 48,733 tumors obtained from pts with bladder, breast, ovarian, pancreas, prostate, thyroid, cervical, hepatobiliary, colorectal (CRC), endometrial, gastric/esophageal (GE), head/neck, renal, non-small cell lung (NSCLC), small cell lung (SCLC), GIST, glioma, melanoma, sarcoma and unknown 1° cancers were reviewed to identify somatic pathogenic mutations (mut) in HR genes ATM, ATRX, BARD1, BLM, BRCA1/2, BRIP1, FANCA/C/D2/E/F/G/L, MRE11A, NBN, PALB2, PTEN, RAD50, RAD51, RAD51B, or WRN. Molecular profiles were generated from tumors submitted to Caris Life Sciences using multiple technologies including next generation sequencing (average read depth 500X). Results: Overall frequency of HR mut among all tumors is 11.61% (5658/48733). Cancer lineages with highest frequency of HR mut are endometrial (38.08%, 1956/5137), glioma (15.90%, 265/1667), ovarian (12.99%, 1151/8862), prostate (11.21%, 77/687), cervix (10.06%, 79/785) & breast (9.66%, 562/5818). Least commonly mutated lineages include GIST (1.50%, 3/200), sarcoma (3.12%, 55/1763), head/neck (3.70%, 24/648), hepatobiliary (4.72%, 39/827) & pancreas (5.05%, 102/2022). Frequencies of HR gene mutations are depicted in Table 1. Conclusions: HR mutations were seen in 11.61% of tumors. While the percentage of HRDef in pancreatic cancer pts is lower than what has been seen in other datasets, the percentage in breast and ovarian cancer, as well as the percentage of other tumors with HRDef, provide a path to employ HRDef-directed therapies such as platinums, but especially PARP inhibitors and newer agents such as ATRX inhibitors.
|HR Mutation||Frequency (%)||Lineages Mutated|
|ATM||14.24||All except (ex) head/neck|
|ATRX||0.91||Breast, cervix, CRC, endometrial, GE, GIST, glioma, melanoma, SCLC, NSCLC, ovarian, sarcoma, unknown 1°|
|BLM||0.21||CRC, GE, melanoma, NSCLC|
|BRCA1||2.70||All ex GIST, renal|
|BRCA2||2.88||All ex renal|
|NBN||0.15||Breast, hepatobiliary, CRC, GE, glioma, NSCLC, ovarian|
|PALB2||0.55||All ex GIST, head/neck, prostate, renal, thyroid|
|PTEN||6.10||All ex GIST|