Abstract
Allele-specific KRAS mutations as prognostic biomarkers in mucinous adenocarcinoma of the appendix and colorectal cancer.
Author
Moh'd M. Khushman
Washington University in St. Louis, Siteman Cancer Center, St. Louis, MO
info_outline
Moh'd M. Khushman, Hassan Mohammed Abushukair, Sanad Alhushki, Michael Iglesia, Kian-Huat Lim, Xiuli Liu, Nikolaos Trikalinos, Rama Suresh, Olivia Aranha, Patrick Grierson, Benjamin R. Tan, Katrina Sophia Pedersen
Full text
Authors
Moh'd M. Khushman
Washington University in St. Louis, Siteman Cancer Center, St. Louis, MO
info_outline
Moh'd M. Khushman, Hassan Mohammed Abushukair, Sanad Alhushki, Michael Iglesia, Kian-Huat Lim, Xiuli Liu, Nikolaos Trikalinos, Rama Suresh, Olivia Aranha, Patrick Grierson, Benjamin R. Tan, Katrina Sophia Pedersen
Organizations
Washington University in St. Louis, Siteman Cancer Center, St. Louis, MO, Jordan University of Science and Technology, Irbid, Jordan, Mut’ah University, Amman, Jordan, Washington University, St. Louis, MO, Washington University School of Medicine, St. Louis, MO, Washington University in St. Louis, St. Louis, MO, Washington University Oncology, St. Louis, MO, Washington University School of Medicine in St. Louis, St. Louis, MO
Abstract Disclosures
Research Funding
No funding sources reported
Background:
Kristen rat sarcoma virus (
KRAS
) mutations (MT) are reported in 40-45% of colorectal cancer (CRC), and they are associated with poor prognosis. In mucinous adenocarcinoma of the appendix (MAAP), which is often treated as CRC due to its rarity,
KRAS
MT are reported in >50% of tumors, and they are associated with favorable prognosis. We explored whether allele-specific
KRAS
MT are associated with overall survival (OS) in stage IV MAAP and CRC.
Methods:
The cBioCancer Genomics Portal was used to obtain genomic data. The prevalence of
KRAS
MT and the OS associated with allele-specific
KRAS
MT were explored in stage IV CRC (MSK, Cancer Cell 2018 cohort) and MAAP (MSK, J Clin Oncol 2022 cohort) patients. Survival analysis was performed using the Kaplan-Meier method with log-rank test comparisons.
Results:
The prevalence of
KRAS
MT in stage IV MAAP (N=149) and CRC (N=1099) was 79.8% and 44.2% respectively. The prevalence of allele-specific
KRAS
MT (G12D, G12V, G13D and G12C) in MAAP/CRC was 42.3% / 12.4%, 18.8% / 9%, 6.7% / 7.7% and 6% / 2.8% respectively. All other
KRAS
MT in MAAP/CRC were seen in 6% and 12.2% respectively. In MAAP, the median OS (mOS) in
KRAS
MT vs.
KRAS
wild-type (WT) was 147m vs. 50m (p=0.003). Compared to the mOS in KRAS WT, the mOS was 147m (p=0.004) in G12D, 74m (p=0.140) in G12V, not reached (NR) (p=0.049) in G13D and 34m (p=0.589) in G12C. In CRC, the mOS in
KRAS
MT vs.
KRAS
WT was 60m vs. 79m (p=0.012). Compared to the mOS in KRAS WT, the mOS was 58m (p=0.249) in G12D, 58m (p=0.015) in G12V, 49m (p=0.002) in G13D and 65m (p=0.437) in G12C. The mOS in MAAP vs. CRC was 50m vs. 79m (p=0.022) in
KRAS
WT, 147m vs. 58m (p=0.02) in G12D, 74m vs. 58m (p=0.34) in G12V, NR vs. 49m (p=0.044) in G13D and 34m vs. 65m (p=0.13) in G12C. The favorable mOS associated with G12D in MAAP remained significant after adjusting for age, grade and TP53 (p=0.028)
Conclusions:
KRAS
MT are more common in MAAP (79.8%) than in CRC (44.2%). In contrast to CRC,
KRAS
MT in MAAP are associated with favorable prognosis. Allele-specific
KRAS
MT are associated with different mOS in MAAP and CRC. The mOS in MAAP with
KRAS
G12D was exceptionally favorable (147m). To our knowledge, this is the first study to explore allele-specific
KRAS
mutations as prognostic biomarkers in MAAP, and adds additional data to support the distinct differences between MAAP and CRC at the molecular level.
Prevalence %
mOS (months )
MAAP (N=149)
CRC (N=1099)
MAAP
CRC
KRAS WT
20.1%
55.8%
50
79
KRAS MT (any)
79.8%
44.2%
147
60
G12D
42.3%
12.4%
147
58
G12V
18.8%
9%
74
58
G13D
6.7%
7.7%
NR
49
G12C
6%
2.8%
34
65
Other MT
6%
12.3%
-
-
2 organizations
Organization
Jordan University of Science and TechnologyOrganization
Mut’ah University