abstract: Pancreatic cancer and a novel MSH2 germline alteration

CONCLUSIONS:

The MSH2 P349L may increase the risk for pancreatic cancer beyond the usual mutations in DNA mismatch repair genes; however, studies of additional families with the identical missense alteration are needed to confirm this initial impression.

Narod: Should All Women With Breast Cancer Be Tested for BRCA Mutations at the Time of Diagnosis?

....For now, perhaps the simplest recommendation is to test women under age 50 years with triple-negative breast cancer and women with a family history of early-onset breast cancer or ovarian cancer......

Recurrent Somatic DICER1 Mutations in Nonepithelial Ovarian Cancers — NEJM

The predicted truncation from a (ovarian) cancer-associated variant of the MSH2 initiation codon alters activity of the MSH2-MSH6 mismatch repair complex

Abstract

Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes. MMR recognizes and repairs DNA mismatches and small insertion/deletion loops. Carriers of MMR gene variants have a high risk of developing colorectal, endometrial, ovarian, and other extracolonic carcinomas. We report on an ovarian cancer patient who carries a germline MSH2 c.1A>C variant which alters the translation initiation codon. Mutations affecting the MSH2 start codon have been described previously for LS-related malignancies. However, the patients often lack a clear family history indicative of LS and their tumors often fail to display microsatellite instability, a hallmark feature of LS...."(technical)

Mutational analysis and clinical correlation of 185 consecutive metastatic colorectal patients: Similarities and differences between colon and rectal patients| 2011 ASCO Abstract

Conclusions:

Rectal and colon patients have similar rates of KRAS and PIK3CA mutations. However, BRAF mutations are more common in colon cancer. NRAS mutations are exclusively found in rectosigmoid cancers and may have a different biology than other colorectal cancers. These data suggest that primary tumor location may provide a means to enrich a population for a genotype-directed study.

full free access: Breast and Ovarian Cancer Risk due to Prevalence of BRCA1 and BRCA2 Variants in Pakistani Population: A Pakistani Database Report

Abstract

Pakistani population has a very rich anthrogeneological background with waves of migration from neighboring regions. Incidence rates of breast and ovarian cancer in Pakistan are on such a rapid rise that it is necessary to check the contributory factors, genetic and nongenetic. An insight into the prevalence data emphasizes the formulation of a BRCA1 and BRCA2 database for the Pakistani population.....

Most of BRCA1 and BRCA2 research has been focused on the Caucasian populations; however, the allelic frequency of higher penetrance genes in the Asian population may be higher than that in Caucasian population.................. cont'd (abstract/full free access)

see full paper for further information 

examples: Figure 3 & 4: (brca 1/brca 2/specific mutations/variants):

Penetrance (mutations) - Wikipedia, the free encyclopedia

Associated terminology

• complete penetrance. The allele is said to have complete penetrance if all individuals who have the disease-causing mutation have clinical symptoms of the disease.
• highly penetrant. If an allele is highly penetrant, then the trait it produces will almost always be apparent in an individual carrying the allele.
• incomplete penetrance or reduced penetrance. Penetrance is said to be reduced or incomplete when some individuals fail to express the trait, even though they carry the allele.
• low penetrance. An allele with low penetrance will only sometimes produce the symptom or trait with which it has been associated at a detectable level. In cases of low penetrance, it is difficult to distinguish environmental from genetic factors.

full free text: Targeted Epigenetic Therapies: The Next Frontier? — J. Natl. Cancer Inst. (includes discussion regarding clear cell/ARIDIa mutation

Targeted Epigenetic Therapies: The Next Frontier?

1. Rabiya S. Tuma

When researchers look for mutations associated with cancer, they often expect to come up with alterations in signaling molecules or transcription factors. But an increasing number of the mutations found are in genes that regulate the epigenome—a system that alters DNA structure and regulates gene activity without changing the nucleotide sequence itself.

On Sept. 8, investigators published two independent reports online—one in Science and one in the New England Journal of Medicine—showing that mutations in an epigenetic regulatory gene, ARID1a, were associated with approximately half of the ovarian clear-cell cancers tested.

OncoMap Gene Sequencing Finds 50 Mutations in Ovarian Tumors : Internal Medicine News

".....The team, testing 203 samples with OncoMap, found mutations of 50 genes in total. Some mutations were in genes previously identified in ovarian cancer, including KRAS, CTNNB1, and PIK3CA. Others were not previously known to occur in this disease, but, importantly, are potential drug targets with existing agents. "It’s not like HER2 in breast cancer where that is found in about 30% of breast cancers – we found many mutations in the ovarian cancer samples and they were infrequent," Dr. Matulonis said in a telephone interview prior to the conference; she noted, however, that OncoMap identified KRAS and PIK3CA mutations as the most common, occurring in about 25% of tumors, and "that was reassuring," as it was in line with expectations..........Dr. Matulonis’ team is now using OncoMap on all new ovarian cancers, including nonserous cancers, diagnosed at Dana-Farber, and she predicted the test will become standard in clinical practice within 6 months to a year..........cont'd

Medical News: BRCA1 Breast Cancer Risk Linked to Other Mutations (more detailed report - Medpage)

Identification of a Danish breast/ovarian cancer family double heterozygote for BRCA1 and BRCA2 mutations

Abstract
Mutations in the two breast cancer susceptibility genes BRCA1 and BRCA2 are associated with increased risk of breast and ovarian cancer. Patients with mutations in both genes are rarely reported and often involve Ashkenazi founder mutations. ......Since the BRCA1 Arg1699Gln mutation is also suggested to be disease-causing, we consider this family double heterozygote for BRCA1 and BRCA2 mutations.