Chromosomal Instability in Near-Diploid Colorectal Cancer: A Link between Numbers and Structure

Chromosomal instability (CIN) plays a crucial role in tumor development and occurs mainly as the consequence of either missegregation of normal chromosomes (MSG) or structural rearrangement (SR). However, little is known about the respective chromosomal targets of MSG and SR and the way these processes combined within tumors to generate CIN. To address these questions, we karyotyped a consecutive series of 96 near-diploid colorectal cancers (CRCs) and distinguished chromosomal changes generated by either MSG or SR in tumor cells. Eighty-three tumors (86%) presented with chromosomal abnormalities that contained both MSGs and SRs to varying degrees whereas all 13 others (14%) showed normal karyotype. Using a maximum likelihood statistical method, chromosomes affected by MSG or SR and likely to represent changes that are selected for during tumor progression were found to be different and mostly mutually exclusive. MSGs and SRs were not randomly associated within tumors, delineating two major pathways of chromosome alterations that consisted of either chromosome gains by MSG or chromosomal losses by both MSG and SR. CRCs showing microsatellite instability (MSI) presented with either normal karyotype or chromosome gains whereas MSS (microsatellite stable) CRCs exhibited a combination of the two pathways. Taken together, these data provide new insights into the respective involvement of MSG and SR in near-diploid colorectal cancers, showing how these processes target distinct portions of the genome and result in specific patterns of chromosomal changes according to MSI status

Copy number alterations and allelic ratio in relation to recurrence of rectal cancer

BACKGROUND: In rectal cancer, total mesorectal excision surgery combined with preoperative (chemo)radiotherapy reduces local recurrence rates but does not improve overall patient survival, a result that may be due to the harmful side effects and/or co-morbidity of preoperative treatment. New biomarkers are needed to facilitate identification of rectal cancer patients at high risk for local recurrent disease. This would allow for preoperative (chemo)radiotherapy to be restricted to high-risk patients, thereby reducing overtreatment and allowing personalized treatment protocols. We analyzed genome-wide DNA copy number (CN) and allelic alterations in 112 tumors from preoperatively untreated rectal cancer patients. Sixty-six patients with local and/or distant recurrent disease were compared to matched controls without recurrence. Results were validated in a second cohort of tumors from 95 matched rectal cancer patients. Additionally, we performed a meta-analysis that included 42 studies reporting on CN alterations in colorectal cancer and compared results to our own data. RESULTS: The genomic profiles in our study were comparable to other rectal cancer studies. Results of the meta-analysis supported the hypothesis that colon cancer and rectal cancer may be distinct disease entities. In our discovery patient study cohort, allelic retention of chromosome 7 was significantly associated with local recurrent disease. Data from the validation cohort were supportive, albeit not statistically significant, of this finding. CONCLUSIONS: We showed that retention of heterozygosity on chromosome 7 may be associated with local recurrence in rectal cancer. Further research is warranted to elucidate the mechanisms and effect of retention of chromosome 7 on the development of local recurrent disease in rectal cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1550-0) contains supplementary material, which is available to authorized users

Y chromosome haplogroups of elite Ethiopian endurance runners

Favourable genetic endowment has been proposed as part of the explanation for the success of East African endurance athletes, but no evidence has yet been presented. The Y chromosome haplogroup distribution of elite Ethiopian athletes (n=62) was compared with that of the general Ethiopian population (n=95) and a control group from Arsi (a region producing a disproportionate number of athletes; n=85). Athletes belonged to three groups: marathon runners (M; n=23), 5–km to 10–km runners (5–10K; n=21) and other track and field athletes (TF; n=18). DNA was extracted from buccal swabs and haplogroups were assigned after the typing of binary markers in multiplexed minisequencing reactions. Frequency differences between groups were assessed by using contingency exact tests and showed that Y chromosome haplogroups are not distributed amongst elite Ethiopian endurance runners in the same proportions as in the general population, with statistically significant (P less than 0.05) differences being found in four of the individual haplogroups. The geographical origins and languages of the athletes and controls suggest that these differences are less likely to be a reflection of population structure and that Y chromosome haplogroups may play a significant role in determining Ethiopian endurance running success

The disappearing microbiota: Diseases of the Western Civilization

The human being is a superorganism composed of human cells and its associated microbiota. Humans did not emerge alone along evolution but in coexistence and intricate metabolic integration with microorganisms. The microorganisms that co-evolve and co-live with humans are called the microbiota. The human gut microbiota is a dynamic taxonomically complex community that participates in several processes related to normal function of the host-microbiota superorganism, maintaining the health status. Changes to the social aspects of the Western civilization and technological developments impacted on the evolutionary host-microbes? association. As a consequence of the disruption to this equilibrium, immunological, endocrine, metabolic and neurological alterations have arisen. Maternal diet, lifestyle, mode of delivery, administration of antibiotics to the mother during pregnancy, early nutrition (breastfeeding or formula) and treatment with antibiotics in newborns are crucial factors that affect microbiota structure. Microbiota and epigenome are involved in the reduced or increased risk to develop different microbiome-associated diseases in adult life.Fil: Salvucci, Emiliano Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias (FCA). Instituto de Ciencia y Tecnología de Alimentos Córdoba (ICYTAC); Argentin