Experiences from treatment-predictive KRAS testing; high mutation frequency in rectal cancers from females and concurrent mutations in the same tumor

Jönsson, MatsLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine (author)

BACKGROUND: KRAS mutations represent key alterations in colorectal cancer development and lead to constitutive EGFR signaling. Since EGFR inhibition represents a therapeutic strategy in advanced colorectal cancer, KRAS mutation analysis has quickly been introduced as a treatment-predictive test.METHODS: We used a real-time PCR based method to determine KRAS mutations in 136 colorectal cancers with mutations identified in 53 (39%) tumors.RESULTS: KRAS mutations were significantly more often found in rectal cancer (21/38, 55%) than in colon cancer (32/98, 33%) (P = 0.02). This finding was explained by marked differences mutation rates in female patients who showed mutations in 33% of the colon cancers and in 67% of the rectal cancers (P = 0.01). Concurrent KRAS mutations were identified in three tumors; two colorectal cancers harbored Gly12Asp/Gly13Asp and Gly12Cys/Gly13Asp and a third tumor carried Gly12Cys/Gly12Asp in an adenomatous component and additionally acquired Gly12Val in the invasive component.CONCLUSION: The demonstration of a particularly high KRAS mutation frequency among female rectal cancer patients suggests that this subset is the least likely to respond to anti-EGFR therapies, whereas the observation of concurrent KRAS mutations imply that repeated KRAS targeting may occur during tumor progression in a subset of colorectal cancers.

Isinger Ekstrand, AnnaLund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)onk-ais (author)
Edekling, ThomasVäxjö Central Hospital (author)
Eberhard, JakobLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Institutionen för kliniska vetenskaper, Malmö,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Department of Clinical Sciences, Malmö(Swepub:lu)kir-jeb (author)
Grabau, DortheLund University,Lunds universitet,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-dgu (author)
Borg, DavidLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-dbo (author)
Nilbert, MefLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-mni (author)
Bröstcancer-genetikSektion I (creator_code:org_t)

In:BMC Clinical Pathology: Springer Science and Business Media LLC9:Oct 15, s. 8-81472-6890

By the author/editor: Jönsson, Mats; Isinger Ekstrand ...; Edekling, Thomas; Eberhard, Jakob; Grabau, Dorthe; Borg, David; show more...; Nilbert, Mef; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.